Femtosecond Laser-Assisted In Situ Keratomileusis Treatment of Residual Refractive Error following Femtosecond Laser-Enabled Keratoplasty.

Purpose:To evaluate the safety and effectiveness of femtosecond laser-assisted in situ keratomileusis (LASIK) in the treatment of residual myopia and astigmatism following femtosecond laser-enabled keratoplasty (FLEK). Design:Retrospective case review. Methods:Chart review of all patients with prior FLEK who subsequently underwent femto-LASIK surgery after full suture removal was performed at the Gavin Herbert Eye Institute at the University of California, Irvine. A total of 14 eyes in 13 patients met this criterion, and their comprehensive examinations performed at standard intervals were reviewed. Main outcome measures include uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) expressed as the logarithm of the minimum angle of resolution (logMAR), manifest refractive astigmatism, and spherical equivalent. Results:From the preoperative visit to the 3 month visit, all 14 eyes significantly improved in UDVA (logMAR, 0.93 ± 0.23 to 0.44 ± 0.32, P = 0.002) with no loss of CDVA (logMAR, 0.26 ± 0.19 to 0.18 ± 0.23, P = 0.50). All 14 eyes showed significant improvement in manifest refractive astigmatism (4.71 ± 1.77 to 2.18 ± 1.45 diopters (D), P = 0.003) and spherical equivalent (-2.57 ± 2.45 to -0.48 ± 0.83 D, P = 0.0007). There were no flap or graft complications as a result of femto-LASIK. Conclusions:Our findings suggest that femto-LASIK on eyes with prior FLEK is safe and effective in improving visual acuity and reducing residual astigmatism

Elevated neoantigen levels in tumors with somatic mutations in the HLA-A, HLA-B, HLA-C and B2M genes.

BackgroundThe major histocompatibility complex class I (MHC-I) molecule is a protein complex that displays intracellular peptides to T cells, allowing the immune system to recognize and destroy infected or cancerous cells. MHC-I is composed of a highly polymorphic HLA-encoded alpha chain that binds the peptide and a Beta-2-microglobulin (B2M) protein that acts as a stabilizing scaffold. HLA mutations have been implicated as a mechanism of immune evasion during tumorigenesis, and B2M is considered a tumor suppressor gene. However, the implications of somatic HLA and B2M mutations have not been fully explored in the context of antigen presentation via the MHC-I molecule during tumor development. To understand the effect that B2M and HLA MHC-I molecule mutations have on mutagenesis, we analyzed the accumulation of mutations in patients from The Cancer Genome Atlas according to their MHC-I molecule mutation status.ResultsSomatic B2M and HLA mutations in microsatellite stable tumors were associated with higher overall mutation burden and a larger fraction of HLA-binding neoantigens when compared to B2M and HLA wild type tumors. B2M and HLA mutations were highly enriched in patients with microsatellite instability. B2M mutations tended to occur relatively early during patients' respective tumor development, whereas HLA mutations were either early or late events. In addition, B2M and HLA mutated patients had higher levels of immune infiltration by natural killer and CD8+ T cells and higher levels of cytotoxicity.ConclusionsOur findings add to a growing body of evidence that somatic B2M and HLA mutations are a mechanism of immune evasion by demonstrating that such mutations are associated with a higher load of neoantigens that should be presented via MHC-I

Essays: Color-blind or Race-conscious Policies

The debate between advocates color blind and race conscious policies has been perennial in the United States since Reconstruction and has recently been resuscitated in the popular press with the publication of Michelle Alexander’s The New Jim Crow: Mass Incarceration in the Age of Color Blindness (2010). Alexander’s book provided support for the race conscious side and students read Nathan Glazer’s Affirmative Discrimination: Ethnic Inequality and Public Policy (1975) for a defense of the color blind side. The debate was framed in an even-handed manner by a selection from Desmond King and Rogers M. Smith’s Still a House Divided: Race and Politics in Obama’s America (2011) , which argues for both approaches under certain circumstances

Perfil epidemiológico dos casos de coqueluche no Brasil nos anos de 2010 a 2014

A Coqueluche é uma doença infecciosa aguda de notificação compulsória causada pela bactéria Bordetella pertussis. Ela acomete o trato respiratório e seu principal sintoma é a tosse paroxística. Essa acomete todas as idades, mas é mais frequente e grave em menores de 1 ano. O objetivo desse trabalho é apresentar a epidemiologia descritiva e a cobertura vacinal no Brasil nos anos de 2010 a 2014, sendo realizado por meio de revisão bibliográfica no contexto epidemiológico. A cobertura vacinal atingiu o preconizado em todos os anos, entretanto este não ocorreu de forma homogênea. Houve um aumento de 1.505% de casos do ano de 2010 a 2014, configurando uma possível reemergência da doença. A causa desse aumento ainda não foi elucidada, porém há hipóteses que relacionam com a melhora diagnóstica, vigilância epidemiológica mais sensível, uma cepa mais virulenta e a redução da imunização após alguns anos da última dose da vacina

Whole-genome functional characterization of RE1 silencers using a modified massively parallel reporter assay.

Transcriptional silencers are under- studied compared with activating elements. By using MPRAduo, Mouri et al. perform a whole-genome functional characterization screen of RE1 silencers and identify REST-binding motif characteristics and cofactor localization required for a functional silencer. They also identify human genetic variants that impact RE1 activity

Caesarean section and risk of unexplained stillbirth in subsequent pregnancy

Background Caesarean section is associated with an increased risk of disorders of placentation in subsequent pregnancies, but effects on the rate of antepartum stillbirth are unknown. We aimed to establish whether previous caesarean delivery is associated with an increased risk of antepartum stillbirth. Methods We linked pregnancy discharge data from the Scottish Morbidity Record (1980–98) and the Scottish Stillbirth and Infant Death Enquiry (1985–98). We estimated the relative risk of antepartum stillbirth in second pregnancies using time-to-event analyses. Findings For 120 633 singleton second births, there were 68 antepartum stillbirths in 17 754 women previously delivered by caesarean section (2–39 per 10 000 women per week) and 244 in 102879 women previously delivered vaginally (1·44; p<0·001). Risk of unexplained stillbirth associated with previous caesarean delivery differed significantly with gestational age (p=0·04); the excess risk was apparent from 34 weeks (hazard ratio 2·23 [95% Cl 1·48–3·36]). Risk was not attenuated by adjustment for maternal characteristics or outcome of the first pregnancy (2·74 [1·74–4·30]). The absolute risk of unexplained stillbirth at or after 39 weeks' gestation was 1·1 per 1000 women who had had a previous caesarean section and 0·5 per 1000 in those who had not. The difference was due mostly to an excess of unexplained stillbirths among women previously delivered by caesarean section. Interpretation Delivery by caesarean section in the first pregnancy could increase the risk of unexplained stillbirth in the second. In women with one previous caesarean delivery, the risk of unexplained antepartum stillbirth at or after 39 weeks' gestation is about double the risk of stillbirth or neonatal death from intrapartum uterine rupture

Nose-to-brain delivery of enveloped RNA - cell permeating peptide nanocomplexes for the treatment of neurodegenerative diseases

This document is the preprint manuscript version of a published work that appeared in final form in Biomaterials, © 2019 Elsevier Ltd. after peer review and technical editing by the publisher. To access the final edited and published work see: https://doi.org/10.1016/j.biomaterials.2019.119657Direct nose-to-brain (N-to-B) delivery enables the rapid transport of drugs to the brain, while minimizing systemic exposure. The objective of this work was to engineer a nanocarrier intended to enhance N-to-B delivery of RNA and to explore its potential utility for the treatment of neurological disorders. Our approach involved the formation of electrostatically driven nanocomplexes between a hydrophobic derivative of octaarginine (r8), chemically conjugated with lauric acid (C12), and the RNA of interest. Subsequently, these cationic nanocomplexes were enveloped (enveloped nanocomplexes, ENCPs) with different protective polymers, i.e. polyethyleneglycol - polyglutamic acid (PEG-PGA) or hyaluronic acid (HA), intended to enhance their stability and mucodiffusion across the olfactory nasal mucosa. These rationally designed ENCPs were produced in bulk format and also using a microfluidics-based technique. This technique enabled the production of a scalable nanoformulation, exhibiting; (i) a unimodal size distribution with a tunable mean size, (ii) the capacity to highly associate (100%) and protect RNA from degradation, (iii) the ability to preserve its physicochemical properties in biorelevant media and prevent the premature RNA release. Moreover, in vitro cell culture studies showed the capacity of ENCPs to interact and be efficiently taken-up by CHO cells. Finally, in vivo experiments in a mouse model of Alzheimer's disease provided evidence of a statistically significant increase of a potentially therapeutic miRNA mimic in the hippocampus area and its further effect on two mRNA targets, following its intranasal administration. Overall, these findings stress the value of the rational design of nanocarriers towards overcoming the biological barriers associated to N-to-B RNA delivery and reveal their potential value as therapeutic strategies in Alzheimer's diseaseThe work was supported by the European B-Smart Consortium, which received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 721058S

Experiences of transition to adult care and readiness to self-manage care in young people with perinatal HIV in England

Background: There are few data on young people’s own experiences of transferring from paediatric to adult care, or readiness to self-manage care. Methods: A total of 132 young people living with perinatal HIV, aged 14–25 years, answered questions about transition experiences. Results: Of the participants, 45 (34%), with a median age of 16 (interquartile range [IQR] 16–17), were in paediatric care, of whom 89% reported that transition discussions had begun, at median age 15 (IQR 14–16) years. Young people in adult care were more likely than those in paediatric care to self manage appointments (90% vs 42% respectively, P < 0.001), and know their antiretroviral therapy (ART) drugs (55% vs 37%, P = 0.033). Knowledge of most recent CD4 T cell count/VL was slightly better for those in adult care (48% vs 31%, P = 0.059); naming side effects of ART was similar (71% vs 60%, P = 0.119). Conclusions: Transition discussions occurred before movement from paediatric to adult care. Further education around ART, potential side effects, and CD4 T cell count/viral load knowledge is required

System to control indoor air quality in energy efficient buildings

This work looks at monitoring air quality in indoor environments through the integration of several sensing technologies into a single robust, reliable and cheap detection platform, which shares air pre-conditioning and electronics. Target gases and detection limits have been set according to recommendations of different agencies in Europe and the US. The system has reached detection limits stated by the OSHA (Occupational Safety and Health Administration) for benzene. The pre-conditioning fluidic platform has also been designed, simulated, fabricated and tested with sensors so the gas flow has been optimized. Field tests in real buildings are being carried out to contrast current measurement procedures and results with the obtained using the device under development. The main aim of the system is to control HVAC (Heat Ventilation and Air Conditioning) in energy-efficient way while keeping a high air quality standard inside the building