Abstract
Background
Recent studies have reported weight gain in virologically suppressed persons living with human immunodeficiency virus (PLWH) switched from older antiretroviral therapy (ART) to ...newer integrase strand transfer inhibitor (INSTI)–based regimens. In this study, we investigated whether weight gain differs among treatment-naive PLWH starting INSTI-based regimens compared to other ART regimens.
Methods
Adult, treatment-naive PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiating INSTI-, protease inhibitor (PI)–, and nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART between January 2007 and June 2016 were included. We used multivariable linear mixed-effects models to generate marginal predictions of weights over time, adjusting for baseline clinical and demographic characteristics. We used restricted cubic splines to relax linearity assumptions and bootstrapping to generate 95% confidence intervals.
Results
Among 1152 ART-naive PLWH, 351 initiated INSTI-based regimens (135 dolutegravir, 153 elvitegravir, and 63 raltegravir), 86% were male, and 49% were white. At ART initiation, median age was 35 years, body mass index was 25.1 kg/m2, and CD4+ T-cell count was 318 cells/μL. Virologic suppression at 18 months was similar between different ART classes. At all examined study time points, weight gain was highest among PLWH starting dolutegravir. At 18 months, PLWH on dolutegravir gained 6.0 kg, compared to 2.6 kg for NNRTIs (P < .05), and 0.5 kg for elvitegravir (P < .05). PLWH starting dolutegravir also gained more weight at 18 months compared to raltegravir (3.4 kg) and PIs (4.1 kg), though these differences were not statistically significant.
Conclusions
Treatment-naive PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens.
This report evaluates the differences in weight gain among treatment-naive persons living with HIV (PLWH) initiating antiretroviral therapy. The results highlight enhanced weight gain among PLWH starting dolutegravir-based therapy and lower weight gain with elvitegravir-based therapy.
Here we use a chromosome-level genome assembly of a prairie rattlesnake (
), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of genome biology and evolution in ...reptiles. We identify the rattlesnake Z Chromosome, including the recombining pseudoautosomal region, and find evidence for partial dosage compensation driven by an evolutionary accumulation of a female-biased up-regulation mechanism. Comparative analyses with other amniotes provide new insight into the origins, structure, and function of reptile microchromosomes, which we demonstrate have markedly different structure and function compared to macrochromosomes. Snake microchromosomes are also enriched for venom genes, which we show have evolved through multiple tandem duplication events in multiple gene families. By overlaying chromatin structure information and gene expression data, we find evidence for venom gene-specific chromatin contact domains and identify how chromatin structure guides precise expression of multiple venom gene families. Further, we find evidence for venom gland-specific transcription factor activity and characterize a complement of mechanisms underlying venom production and regulation. Our findings reveal novel and fundamental features of reptile genome biology, provide insight into the regulation of snake venom, and broadly highlight the biological insight enabled by chromosome-level genome assemblies.
Summary
Fluorescent proteins (FPs) have become essential tools for a growing number of fields in biology. However, such tools have not been widely adopted for use in microalgal research. The aim of ...this study was to express and compare six FPs (blue mTagBFP, cyan mCerulean, green CrGFP, yellow Venus, orange tdTomato and red mCherry) in the popular model microalga Chlamydomonas reinhardtii. To circumvent the transgene silencing that often occurs in C. reinhardtii, the FPs were expressed from the nuclear genome as transcriptional fusions with the sh‐ble antibiotic resistance gene, with the foot and mouth disease virus 2A self‐cleaving sequence placed between the coding sequences. All ble–2A–FPs tested are well‐expressed and efficiently processed to yield mature, unfused FPs that localize throughout the cytoplasm. The fluorescence signals of each FP were detectable in whole cells by fluorescence microplate reader analysis, live‐cell fluorescence microscopy, and flow cytometry. Furthermore, we report a comparative analysis of fluorescence levels relative to auto‐fluorescence for the chosen FPs. Finally, we demonstrate that the ble–2A expression vector may be used to fluorescently label an endogenous protein (α‐tubulin). We show that the mCerulean–α‐tubulin fusion protein localizes to the cytoskeleton and flagella, as expected, and that cells containing this fusion protein had normal cellular function. Overall, our results indicate that, by use of the ble–2A nuclear expression construct, a wide array of FP tools and technologies may be applied to microalgal research, opening up many possibilities for microalgal biology and biotechnology.
We have carried out a near-infrared imaging survey of luminous young stellar outflow candidates using the United Kingdom Infrared Telescope. Observations were obtained through the broad-band K (2.2 ...μm) and narrow-band filters at the wavelengths of H2 v= 1–0 S(1) (2.1218 μm) and Brγ (2.166 μm) lines. 50 regions were imaged with a field of view of 2.2 × 2.2 arcmin2. Several young embedded clusters are unveiled in our near-infrared images. 76 per cent of the objects exhibit H2 emission and 50 per cent or more of the objects exhibit aligned H2 emission features suggesting collimated outflows, many of which are new detections. These observations suggest that disc accretion is probably the leading mechanism in the formation of stars, at least up to late O spectral types. The young stellar objects (YSOs) responsible for many of these outflows are positively identified in our images based on their locations with respect to the outflow lobes, Two-Micron All-Sky Survey colours and association with Midcourse Space Experiment, Infrared Astronomical Satellite, millimetre and radio sources. The close association of molecular outflows detected in CO with the H2 emission features produced by shock excitation by jets from the YSOs suggests that the outflows from these objects are jet-driven. Towards strong radio emitting sources, H2 jets were either not detected or were weak when detected, implying that most of the accretion happens in the pre-ultracompact (pre-UC) H ii phase; accretion and outflows are probably weak when the YSO has advanced to its UC H ii stage.
Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. ...Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg 4 to 6 L in an 80-kg adult during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg ≤2 to 3 L), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.
The partitioning of surface vapor flux (FET) into evaporation (FE) and transpiration (FT) is theoretically possible because of distinct differences in end-member stable isotope composition. In this ...study, we combine high-frequency laser spectroscopy with eddy covariance techniques to critically evaluate isotope flux partitioning of FET over a grass field during a 15 day experiment. Following the application of a 30 mm water pulse, green grass coverage at the study site increased from 0 to 10% of ground surface area after 6 days and then began to senesce. Using isotope flux partitioning, transpiration increased as a fraction of total vapor flux from 0% to 40% during the green-up phase, after which this ratio decreased while exhibiting hysteresis with respect to green grass coverage. Daily daytime leaf-level gas exchange measurements compare well with daily isotope flux partitioning averages (RMSE=0.0018 g m-2 s-1). Overall the average ratio of FT to FET was 29%, where uncertainties in Keeling plot intercepts and transpiration composition resulted in an average of uncertainty of 5% in our isotopic partitioning of FET. Flux-variance similarity partitioning was partially consistent with the isotope-based approach, with divergence occurring after rainfall and when the grass was stressed. Over the average diurnal cycle, local meteorological conditions, particularly net radiation and relative humidity, are shown to control partitioning. At longer time scales, green leaf area and available soil water control FT/FET. Finally, we demonstrate the feasibility of combining isotope flux partitioning and flux-variance similarity theory to estimate water use efficiency at the landscape scale.
Evaporation (E) and transpiration (T) respond differently
to ongoing changes in climate, atmospheric composition, and land use. It is
difficult to partition ecosystem-scale evapotranspiration (ET) ...measurements
into E and T, which makes it difficult to validate satellite data and land
surface models. Here, we review current progress in partitioning E and T and
provide a prospectus for how to improve theory and observations going
forward. Recent advancements in analytical techniques create new
opportunities for partitioning E and T at the ecosystem scale, but their
assumptions have yet to be fully tested. For example, many approaches to
partition E and T rely on the notion that plant canopy conductance and
ecosystem water use efficiency exhibit optimal responses to atmospheric
vapor pressure deficit (D). We use observations from 240 eddy covariance flux
towers to demonstrate that optimal ecosystem response to D is a reasonable
assumption, in agreement with recent studies, but more analysis is necessary
to determine the conditions for which this assumption holds. Another
critical assumption for many partitioning approaches is that ET can be
approximated as T during ideal transpiring conditions, which has been
challenged by observational studies. We demonstrate that T can exceed 95 %
of ET from certain ecosystems, but other ecosystems do not appear to reach
this value, which suggests that this assumption is ecosystem-dependent with
implications for partitioning. It is important to further improve approaches
for partitioning E and T, yet few multi-method comparisons have been
undertaken to date. Advances in our understanding of carbon–water coupling
at the stomatal, leaf, and canopy level open new perspectives on how to
quantify T via its strong coupling with photosynthesis. Photosynthesis can be
constrained at the ecosystem and global scales with emerging data sources
including solar-induced fluorescence, carbonyl sulfide flux measurements,
thermography, and more. Such comparisons would improve our mechanistic
understanding of ecosystem water fluxes and provide the observations
necessary to validate remote sensing algorithms and land surface models to
understand the changing global water cycle.
Transgender youth have low rates of engagement in HIV prevention, shaped in part by experiences of transphobia and lack of access to culturally competent care. Project Moxie tested the feasibility of ...an intervention that provides home-based HIV self-testing coupled with video-chat counseling. A diverse sample of 202 binary and nonbinary transgender youth (TY) were recruited online, and randomized 2:1 to receive the intervention or a control condition of only home-based HIV self-testing. TY were willing to order HIV self-testing kits and report their results. Half of those in the intervention arm opted to use the video-chat counseling and, among those who did, levels of satisfaction were high. Project Moxie demonstrates the ability to recruit TY online and provide them with access to home HIV testing. Further work is required to develop online interventions for youth who do not wish to receive counseling through video-chat formats.
Background Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a ...more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present. Objective We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria. Methods In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements. Results Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness. Conclusion: The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
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