Circadian regulation of glucose, lipid, and energy metabolism in humans.

The circadian system orchestrates metabolism in daily 24-hour cycles. Such rhythms organize metabolism by temporally separating opposing metabolic processes and by anticipating recurring feeding-fasting cycles to increase metabolic efficiency. Although animal studies demonstrate that the circadian system plays a pervasive role in regulating metabolism, it is unclear how, and to what degree, circadian research in rodents translates into humans. Here, we review evidence that the circadian system regulates glucose, lipid, and energy metabolism in humans. Using a range of experimental protocols, studies in humans report circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy expenditure, and appetite. Several of these rhythms peak in the biological morning or around noon, implicating earlier in the daytime is optimal for food intake. Importantly, disruptions in these rhythms impair metabolism and influence the pathogenesis of metabolic diseases. We therefore also review evidence that circadian misalignment induced by mistimed light exposure, sleep, or food intake adversely affects metabolic health in humans. These interconnections among the circadian system, metabolism, and behavior underscore the importance of chronobiology for preventing and treating type 2 diabetes, obesity, and hyperlipidemia

Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review

This narrative review aims to provide an overview of the current literature on thepharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomerof ketamine, for the treatment of treatment-resistant depression (TRD). A literature searchusing Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 toJuly 2019). Product information and www.clinicaltrials.gov were also reviewed. The literaturesearch was limited to human studies published in English. PhaseI, II, and III studies ofintranasal esketamine for TRD were reviewed. About a third of patients with major depressivedisorder fail to achieve remission despite treatment with multiple antidepressants. Thisarticle examines the trials that led to the approval of esketamine in the United States, aswell as other recent studies of esketamine for TRD. The findings from limited phaseIII trialsillustrate that intranasal esketamine is effective and safe in reducing depressive symptomsand achieving clinical response in patients with TRD. The optimum duration and frequency ofuse are not fully understood. Although the nasal spray is a convenient dosage form, its use inpractice may be limited by cost and administrative regulation. While it may prove beneficialto many patients who suffer from TRD, further long-term data are required, along withcomparative trials with the R-isomer (arketamine). In the interim, care and monitoring shouldbe exercised in its use in clinical practice

Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

Impact of Aspheric Monofocal Intraocular Lens Implantation on Uncorrected Intermediate Visual Acuity: a Combined Analysis

Cathleen M McCabe,1 Rachael Peterson,2 Jessie Hull,2 Chandra Bala3 1The Eye Associates, Sarasota, FL, USA; 2Alcon Vision LLC, Fort Worth, TX, USA; 3PersonalEyes, Sydney, NSW, AustraliaCorrespondence: Cathleen M McCabe, The Eye Associates, Sarasota County, 2111 Bee Ridge Road, Sarasota, FL, 34239, USA, Email [email protected]: To evaluate binocular intermediate visual acuity (IVA), depth of focus, and other visual outcomes achieved with a monofocal aspheric intraocular lens (IOL) using pooled data from 2 randomized, double-masked, controlled trials.Patients and Methods: The studies conducted at 32 sites included patients aged ≥ 22 years with bilateral cataracts, preoperative corneal astigmatism 1.0 D, and lens power 18.0– 25.0 D. Patients received bilateral AcrySof IQ IOLs (SN60WF). Primary endpoint data were collected at month 6. Binocular uncorrected and corrected distance visual acuity (UDVA and CDVA) at 4 m, binocular uncorrected and corrected IVA (UIVA and DCIVA) at 66 cm, manifest refraction spherical equivalent (MRSE), and binocular defocus curve at 4 m were assessed under photopic conditions. Validated questionnaires were used to assess spectacle use and quality of vision.Results: Of 233 patients who received SN60WF, 228 had visual acuity data at 6 months. Under photopic conditions, 51% of the eyes had pupils > 4 mm, 40% had pupils 3– 4 mm, and 9% had pupils < 3 mm. Mean ± SD UDVA and CDVA were − 0.019 ± 0.110 and − 0.088 ± 0.082 logMAR, respectively. Mean ± SD UIVA and DCIVA were 0.125 ± 0.145 and 0.196 ± 0.139 logMAR, respectively. UIVA and DCIVA of 20/32 or better were achieved by 83% (188/228) and 71% (162/228) of patients, respectively. Mean ± SD MRSE was − 0.007 ± 0.404 D for the first eye and 0.036 ± 0.371 for the second eye. The defocus curve demonstrated binocular vision of 0.24 logMAR or better from +1.2 to − 1.5 D. Spectacle independence for distance and intermediate vision was reported by 86% and 41% of the patients, respectively. Based on questionnaires, 61%, 79%, and 65% of the patients did not experience starbursts, halos, or glare.Conclusion: A monofocal aspheric IOL (SN60WF) assessed in a large, pooled study provided excellent distance vision and clinically functional intermediate vision.Keywords: Intermediate visual acuity, monofocal aspheric intraocular lens, spectacle Independence, visual qualit

phyloXML: XML for evolutionary biology and comparative genomics

<p>Abstract</p> <p>Background</p> <p>Evolutionary trees are central to a wide range of biological studies. In many of these studies, tree nodes and branches need to be associated (or annotated) with various attributes. For example, in studies concerned with organismal relationships, tree nodes are associated with taxonomic names, whereas tree branches have lengths and oftentimes support values. Gene trees used in comparative genomics or phylogenomics are usually annotated with taxonomic information, genome-related data, such as gene names and functional annotations, as well as events such as gene duplications, speciations, or exon shufflings, combined with information related to the evolutionary tree itself. The data standards currently used for evolutionary trees have limited capacities to incorporate such annotations of different data types.</p> <p>Results</p> <p>We developed a XML language, named phyloXML, for describing evolutionary trees, as well as various associated data items. PhyloXML provides elements for commonly used items, such as branch lengths, support values, taxonomic names, and gene names and identifiers. By using "property" elements, phyloXML can be adapted to novel and unforeseen use cases. We also developed various software tools for reading, writing, conversion, and visualization of phyloXML formatted data.</p> <p>Conclusion</p> <p>PhyloXML is an XML language defined by a complete schema in XSD that allows storing and exchanging the structures of evolutionary trees as well as associated data. More information about phyloXML itself, the XSD schema, as well as tools implementing and supporting phyloXML, is available at <url>http://www.phyloxml.org</url>.</p

Estimating black hole masses of blazars

Estimating black hole masses of blazars is still a big challenge. Because of the contamination of jets, using the previously suggested size -- continuum luminosity relation can overestimate the broad line region (BLR) size and black hole mass for radio-loud AGNs, including blazars. We propose a new relation between the BLR size and $H_{\beta}$ emission line luminosity and present evidences for using it to get more accurate black hole masses of radio-loud AGNs. For extremely radio-loud AGNs such as blazars with weak/absent emission lines, we suggest to use the fundamental plane relation of their elliptical host galaxies to estimate the central velocity dispersions and black hole masses, if their velocity dispersions are not known but the host galaxies can be mapped. The black hole masses of some well-known blazars, such as OJ 287, AO 0235+164 and 3C 66B, are obtained using these two methods and the M - $\sigma$ relation. The implications of their black hole masses on other related studies are also discussed.Comment: 7 pages, invited talk presented in the workshop on Multiwavelength Variability of Blazars (Guangzhou, China, Sept. 22-24, 2010). To be published in the Journal of Astrophysics and Astronom

Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations