Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BackgroundTreatment for both facial and truncal acne has not sufficiently been studied.ObjectivesTo evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne.MethodsIn a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 μg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET.ResultsOf 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit.ConclusionIn this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne

Ring electrode for radio-frequency heating of the cornea: modelling and in vitro experiments

[EN] Radio-frequency thermokeratoplasty (RF-TKP) is a technique used to reshape the cornea curvature by means of thermal lesions using radio-frequency currents. This curvature change allows refractive disorders such as hyperopia to be corrected. A new electrode with ring geometry is proposed for RF-TKP. It was designed to create a single thermal lesion with a full-circle shape. Finite element models were developed, and the temperature distributions in the cornea were analysed for different ring electrode characteristics. The computer results indicated that the maximum temperature in the cornea was located in the vicinity of the ring electrode outer perimeter, and that the lesions had a semi-torus shape. The results also indicated that the electrode thickness, electrode radius and electrode thermal conductivity had a significant influence on the temperature distributions. In addition, in vitro experiments were performed on rabbit eyes. At 5 IN power the lesions were fully circular. Some lesions showed non-uniform characteristics along their circular path. Lesion depth depended on heating duration (60% of corneal thickness for 20s, and 30% for 10s). The results suggest that the critical shrinkage temperature (55-63degreesC) was reached at the central stroma and along the entire circular path in all the cases.Berjano, E.; Saiz Rodríguez, FJ.; Alió, J.; Ferrero, JM. (2003). Ring electrode for radio-frequency heating of the cornea: modelling and in vitro experiments. Medical & Biological Engineering & Computing. 41(6):630-639. https://doi.org/10.1007/BF02349970S630639416Alió, J. L., Ismail, M. M., Artola, A., andPérez-Santonja, J. J. (1997a): ‘Correction of hyperopia induced by photorefractive keratectomy using non-contact Ho: YAG laser thermal keratoplasty’,J. Refract. Surg.,13, pp. 13–16Alió, J. L., Ismail, M. M., andSanchez, J. L. (1997b): ‘Correction of hyperopia with non-contact Ho: YAG laser thermal keratoplasty’,J. Refract. Surg.,13, pp. 17–22Alió, J. 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Intraocular lenses in age-related macular degeneration

Purpose: The aim of this work is to review the lenses, assessing their advantages and disadvantages. We describe a total of seven types of intraocular lenses (IOLs) recommended for age-related macular degeneration (AMD). Methods: We used the PubMed web platform to search for implantable devices in various stages of AMD. We searched for both prospective and retrospective studies and also case reports. Results: Clinical results in AMD patients have been described for a total of seven types of IOLs recommended for AMD: an implantable miniature telescope (IMT), IOL-VIP System, Lipshitz macular implant (LMI), sulcus-implanted Lipshitz macular implant, LMI-SI, Fresnel Prism Intraocular Lens, iolAMD and Scharioth Macula Lens. Conclusions: We conclude that to objectively ascertain the effectiveness and safety of these lenses, further independent clinical studies with longer follow-up data are necessary prior to the general use of these optical devices

From community approaches to single-cell genomics: the discovery of ubiquitous hyperhalophilic Bacteroidetes generalists

The microbiota of multi-pond solar salterns around the world has been analyzed using a variety of culture-dependent and molecular techniques. However, studies addressing the dynamic nature of these systems are very scarce. Here we have characterized the temporal variation during 1 year of the microbiota of five ponds with increasing salinity (from 18% to >40%), by means of CARD-FISH and DGGE. Microbial community structure was statistically correlated with several environmental parameters, including ionic composition and meteorological factors, indicating that the microbial community was dynamic as specific phylotypes appeared only at certain times of the year. In addition to total salinity, microbial composition was strongly influenced by temperature and specific ionic composition. Remarkably, DGGE analyses unveiled the presence of most phylotypes previously detected in hypersaline systems using metagenomics and other molecular techniques, such as the very abundant Haloquadratum and Salinibacter representatives or the recently described low GC Actinobacteria and Nanohaloarchaeota. In addition, an uncultured group of Bacteroidetes was present along the whole range of salinity. Database searches indicated a previously unrecognized widespread distribution of this phylotype. Single-cell genome analysis of five members of this group suggested a set of metabolic characteristics that could provide competitive advantages in hypersaline environments, such as polymer degradation capabilities, the presence of retinal-binding light-activated proton pumps and arsenate reduction potential. In addition, the fairly high metagenomic fragment recruitment obtained for these single cells in both the intermediate and hypersaline ponds further confirm the DGGE data and point to the generalist lifestyle of this new Bacteroidetes group.This work was supported by the projects CGL2012-39627-C03-01 and 02 of the Spanish Ministry of Economy and Competitiveness, which were also co-financed with FEDER support from the European Union. TG group research is funded in part by a grant from the Spanish Ministry of Economy and Competitiveness (BIO2012-37161), a grant from the Qatar National Research Fund grant (NPRP 5-298-3-086) and a grant from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC (grant agreement no. ERC-2012-StG-310325)

Post-operative efficacy, predictability, safety and visual quality of laser corneal refractive surgery: a network meta-analysis

PURPOSE: To compare the post-operative efficacy, predictability, safety and visual quality of all major forms of laser corneal refractive surgeries for correcting myopia. DESIGN: Systematic review and network meta-analysis. METHODS: MEDLINE, EMBASE, Cochrane Library and the US trial registry was conducted up to November 2015. Randomized controlled trials (RCT) reporting in accordance with the eligibility criteria were included in this review. We performed a Bayesian random-effects network meta-analysis. RESULTS: 48 RCTs were identified. For efficacy (uncorrected visual acuity (UCVA)), there were no statistically significant differences between any pair of treatments analyzed. The SUCRA (Surface under the Cumulative Ranking curve) ranking (from best to worst) was: FS-LASIK, LASIK, SMILE, FLEx, PRK, LASEK, Epi-LASIK, T-PRK. For predictability (refractive spherical equivalent (SE)), a statistical significant difference was found when FS-LASIK was compared with LASIK (OR 2.29, 95% CrI 1.20-4.14), PRK (OR 2.16, 95% CrI 1.15-4.03), LASEK (OR 2.09, 95% CrI 1.08-4.55), and Epi-LASIK (OR 2.74, 95% CrI 1.11-6.20). The SUCRA ranking (from best to worst) was: FS-LASIK, T-PRK, LASEK, PRK, LASIK, Epi-LASIK. There were no statistically significant differences in the safety (best spectacle corrected visual acuity (BSCVA)) comparisons. For both post-operative higher order aberrations (HOAs) and contrast sensitivity (CS), there were no statistically significant differences between any pair of treatments analyzed. The SUCRA ranking results show that some corneal surface ablation techniques (PRK and LASEK) rank highest. CONCLUSIONS: This network meta-analysis shows that there were no statistically significant differences in both visual outcomes (efficacy and safety) and visual quality (HOAs and CS). FS-LASIK behaved better in predictability than any other types of surgeries

Radiofrequency Heating of the Cornea: An Engineering Review of Electrodes and Applicators

This paper reviews the different applicators and electrodes employed to create localized heating in the cornea by means of the application of radiofrequency (RF) currents. Thermokeratoplasty (TKP) is probably the best known of these techniques and is based on the principle that heating corneal tissue (particularly the central part of the corneal tissue, i.e. the central stroma) causes collagen to shrink, and hence changes the corneal curvature. Firstly, we point out that TKP techniques are a complex challenge from the engineering point of view, due to the fact that it is necessary to create very localized heating in a precise location (central stroma), within a narrow temperature range (from 58 to 76ºC). Secondly, we describe the different applicator designs (i.e. RF electrodes) proposed and tested to date. This review is planned from a technical point of view, i.e. the technical developments are classified and described taking into consideration technical criteria, such as energy delivery mode (monopolar versus bipolar), thermal conditions (dry versus cooled electrodes), lesion pattern (focal versus circular lesions), and application placement (surface versus intrastromal)

Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits

Purpose: Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model. Methods: A full-depth chondral defect along with subchondral bone injury were originated in the knee joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation. Results: Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface. Conclusions: Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.This study was supported by the Spanish Ministry of Science and Innovation through MAT2010-21611-C03-00 project (including the FEDER financial support), by Conselleria de Educacion (Generalitat Valenciana, Spain) PROMETEO/2011/084 grant, and by CIBER-BBN en Bioingenieria, Biomateriales y Nanomedicina. The work of JLGR was partially supported by funds from the Generalitat Valenciana, ACOMP/2012/075 project. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the - Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Sancho-Tello Valls, M.; Forriol, F.; Gastaldi, P.; Ruiz Sauri, A.; Martín De Llano, JJ.; Novella-Maestre, E.; Antolinos Turpín, CM.... (2015). 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Bacterial Genomes: Habitat Specificity and Uncharted Organisms

The capability and speed in generating genomic data have increased profoundly since the release of the draft human genome in 2000. Additionally, sequencing costs have continued to plummet as the next generation of highly efficient sequencing technologies (next-generation sequencing) became available and commercial facilities promote market competition. However, new challenges have emerged as researchers attempt to efficiently process the massive amounts of sequence data being generated. First, the described genome sequences are unequally distributed among the branches of bacterial life and, second, bacterial pan-genomes are often not considered when setting aims for sequencing projects. Here, we propose that scientists should be concerned with attaining an improved equal representation of most of the bacterial tree of life organisms, at the genomic level. Moreover, they should take into account the natural variation that is often observed within bacterial species and the role of the often changing surrounding environment and natural selection pressures, which is central to bacterial speciation and genome evolution. Not only will such efforts contribute to our overall understanding of the microbial diversity extant in ecosystems as well as the structuring of the extant genomes, but they will also facilitate the development of better methods for (meta)genome annotation

The biogeography of abundant and rare bacterioplankton in the lakes and reservoirs of China.

Bacteria play key roles in the ecology of both aquatic and terrestrial ecosystems; however, little is known about their diversity and biogeography, especially in the rare microbial biosphere of inland freshwater ecosystems. Here we investigated aspects of the community ecology and geographical distribution of abundant and rare bacterioplankton using high-throughput sequencing and examined the relative influence of local environmental variables and regional (spatial) factors on their geographical distribution patterns in 42 lakes and reservoirs across China. Our results showed that the geographical patterns of abundant and rare bacterial subcommunities were generally similar, and both of them showed a significant distance-decay relationship. This suggests that the rare bacterial biosphere is not a random assembly, as some authors have assumed, and that its distribution is most likely subject to the same ecological processes that control abundant taxa. However, we identified some differences between the abundant and rare groups as both groups of bacteria showed a significant positive relationship between sites occupancy and abundance, but the abundant bacteria exhibited a weaker distance-decay relationship than the rare bacteria. Our results implied that rare subcommunities were mostly governed by local environmental variables, whereas the abundant subcommunities were mainly affected by regional factors. In addition, both local and regional variables that were significantly related to the spatial variation of abundant bacterial community composition were different to those of rare ones, suggesting that abundant and rare bacteria may have discrepant ecological niches and may play different roles in natural ecosystems