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Synergistic Anti-Candida Activity of Bengazole A in the Presence of Bengamide A †.
Bengazoles A⁻G from the marine sponge Jaspis sp. exhibit potent in vitro antifungal activity against Candida spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in Candida albicans under both liquid culture and surface culture on Mueller-Hinton agar. Pronounced dose-dependent synergistic antifungal activity was observed with bengazole A in the presence of bengamide A, which is also a natural product from Jaspis sp. The MOA of bengazole A was further explored by monitoring the sterol composition of C. albicans in the presence of sub-lethal concentrations of bengazole A. The GCMS of solvent extracts prepared from liquid cultures of C. albicans in the presence of clotrimazole-a clinically approved azole antifungal drug that suppresses ergosterol biosynthesis by the inhibition of 14α-demethylase-showed reduced cellular ergosterol content and increased concentrations of lanosterol and 24-methylenedihydrolanosterol (a shunt metabolite of ergosterol biosynthesis). No change in relative sterol composition was observed when C. albicans was cultured with bengazole A. These results eliminate an azole-like MOA for the bengazoles, and suggest that another as-yet unidentified mechanism is operative
The Human Connectome Project 7 Tesla retinotopy dataset: Description and population receptive field analysis
The Human Connectome Project 7 Tesla retinotopy dataset: Description and population receptive field analysis
Near-Infrared and Optical Observations of Type Ic SN 2021krf: Luminous Late-time Emission and Dust Formation
We present near-infrared (NIR) and optical observations of the Type Ic
supernova (SN Ic) SN 2021krf obtained between days 13 and 259 at several
ground-based telescopes. The NIR spectrum at day 68 exhibits a rising -band
continuum flux density longward of 2.0 m, and a late-time optical
spectrum at day 259 shows strong [O I] 6300 and 6364 \r{A} emission-line
asymmetry, both indicating the presence of dust, likely formed in the SN
ejecta. We estimate a carbon-grain dust mass of 2 10
M and a dust temperature of 900 - 1200 K associated with this
rising continuum and suggest the dust has formed in SN ejecta. Utilizing the
one-dimensional multigroup radiation hydrodynamics code STELLA, we present two
degenerate progenitor solutions for SN 2021krf, characterized by C-O star
masses of 3.93 and 5.74 M, but with the same best-fit Ni mass
of 0.11 M for early times (0-70 days). At late times (70-300 days),
optical light curves of SN 2021krf decline substantially more slowly than that
expected from Co radioactive decay. Lack of H and He lines in the
late-time SN spectrum suggests the absence of significant interaction of the
ejecta with the circumstellar medium. We reproduce the entire bolometric light
curve with a combination of radioactive decay and an additional powering source
in the form of a central engine of a millisecond pulsar with a magnetic field
smaller than that of a typical magnetar.Comment: Accepted for publication in ApJ, 27 pages, 21 figures, 6 tables.
Previous arXiv submission (arXiv:2211.00205) replaced after acceptanc
Development and Initial Validation of the PEG, a Three-item Scale Assessing Pain Intensity and Interference
Inadequate pain assessment is a barrier to appropriate pain management, but single-item “pain screening” provides limited information about chronic pain. Multidimensional pain measures such as the Brief Pain Inventory (BPI) are widely used in pain specialty and research settings, but are impractical for primary care. A brief and straightforward multidimensional pain measure could potentially improve initial assessment and follow-up of chronic pain in primary care.
To develop an ultra-brief pain measure derived from the BPI.
Development of a shortened three-item pain measure and initial assessment of its reliability, validity, and responsiveness.
We used data from 1) a longitudinal study of 500 primary care patients with chronic pain and 2) a cross-sectional study of 646 veterans recruited from ambulatory care.
Selected items assess average pain intensity (P), interference with enjoyment of life (E), and interference with general activity (G). Reliability of the three-item scale (PEG) was α = 0.73 and 0.89 in the two study samples. Overall, construct validity of the PEG was good for various pain-specific measures (r = 0.60–0.89 in Study 1 and r = 0.77–0.95 in Study 2), and comparable to that of the BPI. The PEG was sensitive to change and differentiated between patients with and without pain improvement at 6 months.
We provide strong initial evidence for reliability, construct validity, and responsiveness of the PEG among primary care and other ambulatory clinic patients. The PEG may be a practical and useful tool to improve assessment and monitoring of chronic pain in primary care
Economic Returns to Investment in AIDS Treatment in Low and Middle Income Countries
Since the early 2000s, aid organizations and developing country governments have invested heavily in AIDS treatment. By 2010, more than five million people began receiving antiretroviral therapy (ART) – yet each year, 2.7 million people are becoming newly infected and another two million are dying without ever having received treatment. As the need for treatment grows without commensurate increase in the amount of available resources, it is critical to assess the health and economic gains being realized from increasingly large investments in ART. This study estimates total program costs and compares them with selected economic benefits of ART, for the current cohort of patients whose treatment is cofinanced by the Global Fund to Fight AIDS, Tuberculosis and Malaria. At end 2011, 3.5 million patients in low and middle income countries will be receiving ART through treatment programs cofinanced by the Global Fund. Using 2009 ART prices and program costs, we estimate that the discounted resource needs required for maintaining this cohort are 12 to $34 billion through increased labor productivity, averted orphan care, and deferred medical treatment for opportunistic infections and end-of-life care. Under alternative assumptions regarding the labor productivity effects of HIV infection, AIDS disease, and ART, the monetary benefits range from 81 percent to 287 percent of program costs over the same period. These results suggest that, in addition to the large health gains generated, the economic benefits of treatment will substantially offset, and likely exceed, program costs within 10 years of investment
Associations of fish oil and vitamin B and E supplementation with cardiovascular outcomes and mortality in people receiving haemodialysis: a review
The Gravity Collective: A Search for the Electromagnetic Counterpart to the Neutron Star-Black Hole Merger GW190814
We present optical follow-up imaging obtained with the Katzman Automatic
Imaging Telescope, Las Cumbres Observatory Global Telescope Network, Nickel
Telescope, Swope Telescope, and Thacher Telescope of the LIGO/Virgo
gravitational wave (GW) signal from the neutron star-black hole (NSBH) merger
GW190814. We searched the GW190814 localization region (19 deg for the
90th percentile best localization), covering a total of 51 deg and 94.6%
of the two-dimensional localization region. Analyzing the properties of 189
transients that we consider as candidate counterparts to the NSBH merger,
including their localizations, discovery times from merger, optical spectra,
likely host-galaxy redshifts, and photometric evolution, we conclude that none
of these objects are likely to be associated with GW190814. Based on this
finding, we consider the likely optical properties of an electromagnetic
counterpart to GW190814, including possible kilonovae and short gamma-ray burst
afterglows. Using the joint limits from our follow-up imaging, we conclude that
a counterpart with an -band decline rate of 0.68 mag day, similar to
the kilonova AT 2017gfo, could peak at an absolute magnitude of at most
mag (50% confidence). Our data are not constraining for ''red'' kilonovae and
rule out ''blue'' kilonovae with (30% confidence). We
strongly rule out all known types of short gamma-ray burst afterglows with
viewing angles 17 assuming an initial jet opening angle of
and explosion energies and circumburst densities similar to
afterglows explored in the literature. Finally, we explore the possibility that
GW190814 merged in the disk of an active galactic nucleus, of which we find
four in the localization region, but we do not find any candidate counterparts
among these sources.Comment: 86 pages, 9 figure
A framework for human microbiome research
A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies