Collagen Crosslinking Reagent Utilized to Modify the Mechanical Properties of the Soft Palate in Equine Snoring and Apnea Applications

Snoring is a sleep disruption that can lead to obstructive sleep apnea (OSA), which interrupts breathing by obstructing the airway. Injecting a protein crosslinker, such as genipin, into the soft palate could decrease the severity of snoring and OSA by stiffening the soft palate. Equine soft palates modeled human palates due to a high incidence of awake snoring and apnea. The pilot in vivo study treated six horses with two 100 mM injections of the buffered genipin reagent. The efficacy phase horses underwent respiratory audio recordings to document snoring changes using Matlab and ImageJ in the time and frequency domains. Histological analysis was completed on the safety phase palates post treatment. All horses were successfully treated with the genipin injections. At least one horse showed high frequency amplitude reductions, and all horses had low frequency amplitude reductions, correlating to a reduction in palatal displacement and snoring loudness. One efficacy horse appears to have been completely cured. The histological analysis presented tissue damage, mucosal tissue damage, and mild inflammation due to palate expansion and errant injections. Different injection volumes and techniques should be investigated next. Applying this treatment to human studies for snoring and OSA applications is the ultimate goal

Ethical Approaches to Mandating Influenza Vaccinations for Local Health Department Workforce in Georgia

Background: The seasonal influenza illness occurs every year in the United States during the cooler months from October to April, sometimes lasting longer. Although certain populations are more susceptible to this condition, data have shown that otherwise healthy individuals have experienced alarming rates of morbidity and mortality associated with these infections. Despite the CDC’s recommendation for influenza vaccination for all HCWs, compliance have been lagging among local health departments’ workforce. This practice arguably exposes a wide cross section of the U.S. population to the flu, while being served in these facilities. The utilitarian approach provides a framework to examine the ethical implications to the public of mandating influenza vaccination for these employees. Methods: A systematic review of peer-reviewed literature was conducted to address the following research questions: 1) Do local public health departments in Georgia mandate annual influenza vaccinations?  2) What are the ethical considerations for mandating influenza vaccinations for public health employees? and 3) What are the ethical considerations for mandating influenza vaccinations for the community? Twenty-five articles were included in the review. Results: Descriptive analysis shows that there is no mandatory vaccination policy in place for state or local departments in health in the state of Georgia. Most of the literature available relates to policy implementation within acute or long-term care facilities. A systematic review of mandatory influenza vaccination for public health workers focused on four areas: theoretical approaches to increase influenza vaccination coverage and support of, opposition to, and alternative strategies for influenza vaccinations. Conclusions: The utilitarian approach is sufficient for the influenza vaccination policy- making strategies and in the ethical approaches of mandating influenza vaccinations for local health department workforce in Georgia if need be, for vaccination targets are to be achieved

Interpreting high [O III]/H β ratios with maturing starbursts

Star-forming galaxies at high redshift show ubiquitously high-ionization parameters, as measured by the ratio of optical emission lines. We demonstrate that local (z < 0.2) sources selected as Lyman break analogues also manifest high line ratios with a typical [O III]/Hβ=3.36+0.14−0.04 – comparable to all but the highest ratios seen in star-forming galaxies at z ∼ 2–4. We argue that the stellar population synthesis code BPASS can explain the high-ionization parameters required through the ageing of rapidly formed star populations, without invoking any AGN contribution. Binary stellar evolution pathways prolong the age interval over which a starburst is likely to show elevated line ratios, relative to those predicted by single stellar evolution codes. As a result, model galaxies at near-solar metallicities and with ages of up to ∼100 Myr after a starburst typically have a line ratio [O III]/Hβ ∼ 3, consistent with those seen in Lyman break galaxies and local sources with similar star formation densities. This emphasises the importance of including binary evolution pathways when simulating the nebular line emission of young or bursty stellar populations

Central retinal vein occlusion 36-month outcomes with anti-vascular endothelial growth factors: the Fight Retinal Blindness! registry

PURPOSE To analyze the 3-year outcomes in a broad population of patients starting vascular endothelial growth factor (VEGF) inhibitors for central retinal vein occlusion (CRVO) in routine clinical practice. DESIGN Observational database study PARTICIPANTS: 527 treatment-naïve CRVO eyes that commenced VEGF inhibitors between December 1, 2010-2018 tracked in the Fight Retinal Blindness! registry. METHODS Longitudinal models were used to plot changes in visual acuity (VA) and central subfield thickness (CST). MAIN OUTCOME MEASURES Mean change in VA from baseline to 36 months, injections, visits, completion, switching and suspensions of therapy >180 days at final review. RESULTS Overall (527 eyes) mean VA change (95% CI) was +10 (7, 12) letters, 37% had final VA ≥70 and 30% ≤35 letters, mean CST changed -306μm. Completers (257/527, 49%) had mean 36-month changes in VA and CST of +12 letters and -324μm with a median of 18 injections at 26 visits. The adjusted mean VA change was similar with each VEGF inhibitor (mean, +11.4 letters) despite a greater reduction in CST with aflibercept (-310μm) vs. ranibizumab (-258μm) vs. bevacizumab (-216μm; P 73 letters, 42/527, 8%) lost 7 letters. Switching (160/527, 30%) was most often to aflibercept (79 eyes). Using suspensions and discontinuation reasons we identified similar proportions had ceased therapy (154/527, 29%) as were still receiving it at 36 months (165/527, 31%). Only 62/527 eyes (12%) had resolution of macular edema without treatment for over 6 months. CONCLUSIONS Patients with CRVO that commenced VEGF inhibitors in routine care for whom follow-up was available had VA improvements of around 12 letters at three years, but with more than 50% lost to follow the VA outcome for the entire group is likely worse. The choice of VEGF inhibitor influenced CST but not VA outcomes. We estimate that around half of eyes were still receiving injections after 36 months

Atypical functional connectivity during unfamiliar music listening in children with autism

Background: Atypical processing of unfamiliar, but less so familiar, stimuli has been described in Autism Spectrum Disorder (ASD), in particular in relation to face processing. We examined the construct of familiarity in ASD using familiar and unfamiliar songs, to investigate the link between familiarity and autism symptoms, such as repetitive behavior. Methods: Forty-eight children, 24 with ASD (21 males, mean age = 9.96 years ± 1.54) and 24 typically developing (TD) controls (21 males, mean age = 10.17 ± 1.90) completed a music familiarity task using individually identified familiar compared to unfamiliar songs, while magnetoencephalography (MEG) was recorded. Each song was presented for 30 s. We used both amplitude envelope correlation (AEC) and the weighted phase lag index (wPLI) to assess functional connectivity between specific regions of interest (ROI) and non-ROI parcels, as well as at the whole brain level, to understand what is preserved and what is impaired in familiar music listening in this population. Results: Increased wPLI synchronization for familiar vs. unfamiliar music was found for typically developing children in the gamma frequency. There were no significant differences within the ASD group for this comparison. During the processing of unfamiliar music, we demonstrated left lateralized increased theta and beta band connectivity in children with ASD compared to controls. An interaction effect found greater alpha band connectivity in the TD group compared to ASD to unfamiliar music only, anchored in the left insula.Conclusion: Our results revealed atypical processing of unfamiliar songs in children with ASD, consistent with previous studies in other modalities reporting that processing novelty is a challenge for ASD. Relatively typical processing of familiar stimuli may represent a strength and may be of interest to strength-based intervention planning.info:eu-repo/semantics/publishedVersio

Parallactic Motion for Companion Discovery: An M-Dwarf Orbiting Alcor

The A5V star Alcor has an M3-M4 dwarf companion, as evidenced by a novel astrometric technique. Imaging spectroscopy combined with adaptive optics coronagraphy allowed for the detection and spectrophotometric characterization of the point source at a contrast of ~6 J- and H-band magnitudes and separation of 1'' from the primary star. The use of an astrometric pupil plane grid allowed us to determine the projected separations between the companion and the coronagraphically occulted primary star to ≤3 mas precision at two observation epochs. Our measurements demonstrate common parallactic and proper motion over the course of 103 days, significantly shorter than the period of time needed for most companion confirmations through proper motion measurements alone. This common parallax method is potentially more rigorous than common proper motion, ensuring that the neighboring bodies lie at the same distance, rather than relying on the statistical improbability that two objects in close proximity to each other on the sky move in the same direction. The discovery of a low-mass (~0.25 M_☉) companion around a bright (V = 4.0 mag), nearby (d= 25 pc) star highlights a region of binary star parameter space that to date has not been fully probed

The evolution of irradiance detection: melanopsin and the non-visual opsins

Circadian rhythms are endogenous 24 h cycles that persist in the absence of external time cues. These rhythms provide an internal representation of day length and optimize physiology and behaviour to the varying demands of the solar cycle. These clocks require daily adjustment to local time and the primary time cue (zeitgeber) used by most vertebrates is the daily change in the amount of environmental light (irradiance) at dawn and dusk, a process termed photoentrainment. Attempts to understand the photoreceptor mechanisms mediating non-image-forming responses to light, such as photoentrainment, have resulted in the discovery of a remarkable array of different photoreceptors and photopigment families, all of which appear to use a basic opsin/vitamin A-based photopigment biochemistry. In non-mammalian vertebrates, specialized photoreceptors are located within the pineal complex, deep brain and dermal melanophores. There is also strong evidence in fish and amphibians for the direct photic regulation of circadian clocks in multiple tissues. By contrast, mammals possess only ocular photoreceptors. However, in addition to the image-forming rods and cones of the retina, there exists a third photoreceptor system based on a subset of melanopsin-expressing photosensitive retinal ganglion cells (pRGCs). In this review, we discuss the range of vertebrate photoreceptors and their opsin photopigments, describe the melanopsin/pRGC system in some detail and then finally consider the molecular evolution and sensory ecology of these non-image-forming photoreceptor systems

Identification of Histone H3 Lysine 36 Acetylation as a Highly Conserved Histone Modification

Histone lysine (K) acetylation is a major mechanism by which cells regulate the structure and function of chromatin, and new sites of acetylation continue to be discovered. Here we identify and characterize histone H3K36 acetylation (H3K36ac). By mass spectrometric analyses of H3 purified from Tetrahymena thermophila and Saccharomyces cerevisiae (yeast), we find that H3K36 can be acetylated or methylated. Using an antibody specific to H3K36ac, we show that this modification is conserved in mammals. In yeast, genome-wide ChIP-chip experiments show that H3K36ac is localized predominantly to the promoters of RNA polymerase II-transcribed genes, a pattern inversely related to that of H3K36 methylation. The pattern of H3K36ac localization is similar to that of other sites of H3 acetylation, including H3K9ac and H3K14ac. Using histone acetyltransferase complexes purified from yeast, we show that the Gcn5-containing SAGA complex that regulates transcription specifically acetylates H3K36 in vitro. Deletion of GCN5 completely abolishes H3K36ac in vivo. These data expand our knowledge of the genomic targets of Gcn5, show H3K36ac is highly conserved, and raise the intriguing possibility that the transition between H3K36ac and H3K36me acts as an “acetyl/methyl switch” governing chromatin function along transcription units

Organismal Differences in Post-translational Modifications in Histones H3 and H4

Post-translational modifications (PTMs) of histones play an important role in many cellular processes, notably gene regulation. Using a combination of mass spectrometric and immunobiochemical approaches, we show that the PTM profile of histone H3 differs significantly among the various model organisms examined. Unicellular eukaryotes, such as Saccharomyces cerevisiae (yeast) and Tetrahymena thermophila (Tet), for example, contain more activation than silencing marks as compared with mammalian cells (mouse and human), which are generally enriched in PTMs more often associated with gene silencing. Close examination reveals that many of the better-known modified lysines (Lys) can be either methylated or acetylated and that the overall modification patterns become more complex from unicellular eukaryotes to mammals. Additionally, novel species-specific H3 PTMs from wild-type asynchronously grown cells are also detected by mass spectrometry. Our results suggest that some PTMs are more conserved than previously thought, including H3K9me1 and H4K20me2 in yeast and H3K27me1, -me2, and -me3 in Tet. On histone H4, methylation at Lys-20 showed a similar pattern as H3 methylation at Lys-9, with mammals containing more methylation than the unicellular organisms. Additionally, modification profiles of H4 acetylation were very similar among the organisms examined

The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery

&lt;p&gt;Background: The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans.&lt;/p&gt; &lt;p&gt;Results: Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates.&lt;/p&gt; &lt;p&gt;Conclusions: The H. contortus genome and transcriptome provides an essential platform for postgenomic research in this and other important strongylid parasites. &lt;/p&gt