The epidemiology of invasive fungal infections (IFIs) in immunocompromised individuals has changed over the last few decades, partially due to the increased use of antifungal agents to prevent IFIs. ...Although this strategy has resulted in an overall reduction in IFIs, a subset of patients develop breakthrough IFIs with substantial morbidity and mortality in this population. Here, we review the most significant risk factors for breakthrough IFIs in haematology patients, solid organ transplant recipients, and patients in the intensive care unit, focusing particularly on host factors, and highlight areas that require future investigation.
The organization of molecules into cells is believed to have been critical for the emergence of living systems. Early protocells likely consisted of RNA functioning inside vesicles made of simple ...lipids. However, little is known about how encapsulation would affect the activity and folding of RNA. Here we find that confinement of the malachite green RNA aptamer inside fatty acid vesicles increases binding affinity and locally stabilizes the bound conformation of the RNA. The vesicle effectively 'chaperones' the aptamer, consistent with an excluded volume mechanism due to confinement. Protocellular organization thereby leads to a direct benefit for the RNA. Coupled with previously described mechanisms by which encapsulated RNA aids membrane growth, this effect illustrates how the membrane and RNA might cooperate for mutual benefit. Encapsulation could thus increase RNA fitness and the likelihood that functional sequences would emerge during the origin of life.
Background
Caregivers of patients undergoing hematopoietic stem cell transplantation (HCT) experience an immense caregiving burden before, during, and after HCT.
Methods
We conducted an unblinded, ...randomized trial of a psychosocial intervention (BMT‐CARE) for caregivers of patients undergoing autologous and allogeneic HCT at Massachusetts General Hospital. Caregivers were randomly assigned to BMT‐CARE or usual care. BMT‐CARE was tailored to the HCT trajectory and integrated treatment‐related education and self‐care with cognitive‐behavioral skills to promote coping. Caregivers assigned to BMT‐CARE met with a trained interventionist (a psychologist or a social worker) in person, via telephone, or via videoconferencing for 6 sessions starting before HCT and continuing up to day +60 after HCT. The primary endpoint was feasibility, which was defined as at least 60% of eligible caregivers enrolling and completing 50% or more of the intervention sessions. We assesed caregiver quality of life (QOL; Caregiver Oncology Quality of Life Questionnaire), caregiving burden (Caregiver Reaction Assessment), psychological distress (Hospital Anxiety and Depression Scale), self‐efficacy (Cancer Self‐Efficacy Scale–Transplant), and coping (Measures of Current Status) at baseline and 30 and 60 days after HCT. We used mixed linear effect models to assess the effect of BMT‐CARE on outcomes longitudinally.
Results
We enrolled 72.5% of eligible caregivers (100 of 138), and 80% attended 50% or more of the intervention sessions. Caregivers randomized to BMT‐CARE reported improved QOL (B = 6.11; 95% CI, 3.50‐8.71; P < .001), reduced caregiving burden (B = –6.02; 95% CI, –8.49 to –3.55; P < .001), lower anxiety (B = –2.18; 95% CI, –3.07 to –1.28; P < .001) and depression symptoms (B = –1.23; 95% CI, –1.92 to –0.54; P < .001), and improved self‐efficacy (B = 7.22; 95% CI, 2.40‐12.03; P = .003) and coping skills (B = 4.83; 95% CI, 3.04‐6.94; P < .001) in comparison with the usual‐care group.
Conclusions
A brief multimodal psychosocial intervention tailored for caregivers of HCT recipients is feasible and may improve QOL, mood, coping, and self‐efficacy while reducing the caregiving burden during the acute HCT period.
In this randomized clinical trial of 100 caregivers of patients undergoing hematopoietic stem cell transplantation (HCT), a brief psychosocial intervention (BMT‐CARE) is found to be feasible with high enrollment and retention rates and to lead to improvements in caregiver quality of life, psychological distress, coping, and self‐efficacy while reducing the caregiving burden during the acute HCT period. Thus, BMT‐CARE is a promising intervention and should be tested in future multisite trials.
Viruses represent the most abundant life forms on the planet. Recent experimental and computational improvements have led to a dramatic increase in the number of viral genome sequences identified ...primarily from metagenomic samples. As a result of the expanding catalog of metagenomic viral sequences, there exists a need for a comprehensive computational platform integrating all these sequences with associated metadata and analytical tools. Here we present IMG/VR (https://img.jgi.doe.gov/vr/), the largest publicly available database of 3908 isolate reference DNA viruses with 264 413 computationally identified viral contigs from >6000 ecologically diverse metagenomic samples. Approximately half of the viral contigs are grouped into genetically distinct quasi-species clusters. Microbial hosts are predicted for 20 000 viral sequences, revealing nine microbial phyla previously unreported to be infected by viruses. Viral sequences can be queried using a variety of associated metadata, including habitat type and geographic location of the samples, or taxonomic classification according to hallmark viral genes. IMG/VR has a user-friendly interface that allows users to interrogate all integrated data and interact by comparing with external sequences, thus serving as an essential resource in the viral genomics community.
The surface air warming over the Arctic has been almost twice as much as the global average in recent decades. In this region, unprecedented amounts of smoldering peat fires have been identified as a ...major emission source of climate-warming agents. While much is known about greenhouse gas emissions from these fires, there is a knowledge gap on the nature of particulate emissions and their potential role in atmospheric warming. Here, we show that aerosols emitted from burning of Alaskan and Siberian peatlands are predominantly brown carbon (BrC) – a class of visible light-absorbing organic carbon (OC) – with a negligible amount of black carbon content. The mean fuel-based emission factors for OC aerosols ranged from 3.8 to 16.6 g kg−1. Their mass absorption efficiencies were in the range of 0.2–0.8 m2 g−1 at 405 nm (violet) and dropped sharply to 0.03–0.07 m2 g−1 at 532 nm (green), characterized by a mean Ångström exponent of ≈ 9. Electron microscopy images of the particles revealed their morphologies to be either single sphere or agglomerated “tar balls”. The shortwave top-of-atmosphere aerosol radiative forcing per unit optical depth under clear-sky conditions was estimated as a function of surface albedo. Only over bright surfaces with albedo greater than 0.6, such as snow cover and low-level clouds, the emitted aerosols could result in a net warming (positive forcing) of the atmosphere.
The eastern China seas are some of the largest marginal seas in the world, where high primary productivity and phytoplankton blooms are often observed. However, little is known about their systematic ...variation of phytoplankton blooms on large spatial and long temporal scales due to the difficulty of monitoring bloom events by field measurement. In this study, we investigated the seasonal and interannual variability and long-term changes in phytoplankton blooms in the eastern China seas using a 14 yr (1998–2011) time series of satellite ocean colour data. To ensure a proper satellite dataset to figure out the bloom events, we validated and corrected the satellite-derived chlorophyll concentration (chl a) using extensive in situ datasets from two large cruises. The correlation coefficients between the satellite retrieval data and the in situ chl a on the logarithmic scale were 0.85 and 0.72 for the SeaWiFS and Aqua/MODIS data, respectively. Although satellites generally overestimate the chl a, especially in highly turbid waters, both the in situ and satellite data show that the overestimation of satellite-derived chl a has an upper limit value (10 μg L−1), which can be used as a threshold for the identification of phytoplankton blooms to avoid the false blooms resulting from turbid waters. Taking 10 μg L−1 as the threshold, we present the spatial-temporal variability of phytoplankton blooms in the eastern China seas over the past 14 yr. Most blooms occur in the Changjiang Estuary and along the coasts of Zhejiang, with a maximal frequency of 20% (about 73 days per year). The coasts of the northern Yellow Sea and the Bohai Sea also have high-frequency blooms (up to 20%). The blooms show significant seasonal variation, with most occurring in spring (April–June) and summer (July–September). The study also revealed a doubling in bloom intensity in the Yellow Sea and Bohai Sea during the past 14 yr. The nutrient supply in the eastern China seas might be a major controlling factor in bloom variation. The time series in situ nutrient datasets show that both the nitrate and phosphate concentrations increased more than twofold between 1998 and 2005 in the Yellow Sea. This might be the reason for the doubling of the bloom intensity index in the Yellow Sea and Bohai Sea. In contrast, there has been no significant long-term increase or decrease in the Changjiang Estuary, which might be regulated by the Changjiang River discharge. These results offer a foundation for the study of the influence of phytoplankton blooms on the carbon flux estimation and biogeochemical processes in the eastern China seas.
The numerical integration of particle trajectories in curved spacetimes is fundamental for obtaining realistic models of the particle dynamics around massive compact objects such as black holes and ...neutron stars. Generalized algorithms capable of handling generic metrics are required for studies of both standard (Schwarzschild and Kerr metrics) and nonstandard (e.g., Schwarzschild metric plus nonclassical perturbations or multiple black hole metrics) spacetimes. The most commonly employed explicit numerical schemes (e.g., Runge-Kutta) are incapable of producing highly accurate results at critical points, e.g., in the regions close to the event horizon where gravity causes extreme curvature of the spacetime, at an acceptable computational cost. Here we describe a generalized algorithm for the numerical integration of time-like (massive particles) and null (photons) geodesics in any given 3 + 1 split spacetime. We introduce a new, exactly energy-conserving implicit integration scheme based on the preservation of the underlying Hamiltonian, and we compare its properties with a standard fourth-order Runge-Kutta explicit scheme and an implicit midpoint scheme. We test the numerical performance of the three schemes against analytic solutions of particle and photon orbits in Schwarzschild and Kerr spacetimes. We also prove the versatility of our framework in handling more exotic metrics, such as Morris-Thorne wormholes and quantum-perturbed Schwarzschild black holes. The generalized approach is also discussed in the perspective of future extensions to more complex particle dynamics, e.g., the addition of the Lorentz force acting on charged particles, which allows for test particle diagnostics in GRMHD simulations.
There are three broad groups of non-Aspergillus moulds: the mucormycetes, the hyalohyphomycetes and the phaeohyphomycetes. Infections with these pathogens are increasingly reported, particularly in ...the context of increasing use of immunosuppressant agents and improved diagnostics. The epidemiology of non-Aspergillus mould infections varies with geography, climate and level of immunosuppression. Skin and soft-tissue infections are the predominant presentation in the immunocompetent host and pulmonary and other invasive infections in the immunocompromised host. The more common non-Aspergillus moulds include Rhizopus, Mucor, Fusarium and Scedosporium species; however, other emerging pathogens are Rasamsonia and Verruconis species, which are discussed in this article. Outbreaks of non-Aspergillus mould infections have been increasingly reported, with contaminated medical supplies and natural disasters as common sources. Currently culture and other conventional diagnostic methods are the cornerstone of diagnosis. Molecular methods to directly detect and identify mould pathogens in tissue and body fluids are increasingly used.
Summary
What is known and objective
Febuxostat is recommended as an alternative drug for gouty patients with a history of allopurinol hypersensitivity or carrying the HLA‐B*5801 allele.
Case summary
...An 81‐year‐old man with the medical history of gout presented to our clinic with generalized rashes for 2 days. After taking febuxostat for 2 days, he developed generalized skin rash with high fever. Laboratory tests showed elevated liver enzymes and acute kidney injury.
What is Known and Objective
This is the first identified case of febuxostat‐associated DRESS. Febuxostat should be withdrawn immediately when DRESS is observed to avoid further serious complications.
Time course of liver function tests.
Multiple myeloma (MM) is incurable in virtually all patients due to the presence of innate and emergent drug-resistance. To identify potential drug resistance mechanisms in MM we used iTRAQ (isobaric ...tags for relative and absolute quantitation) mass spectrometry to compare protein expression profiles of drug-resistant (RPMI 8226-R5) and sensitive (RPMI 8226-S) isogenic cell lines. We identified selective overexpression of myristoylated alanine-rich C-kinase substrate (MARCKS) in drug-resistant R5 cells. MARCKS overexpression was also observed in several drug-resistant human myeloma cell lines (HMCLs) and in drug-resistant primary MM samples. Functionally, inhibition of MARCKS phosphorylation by enzastaurin or knockdown of the gene by RNAi significantly enhanced the sensitivity of resistant HMCLs and primary MM samples to bortezomib and to other anti-myeloma drugs, providing evidence that MARCKS can modulate drug response. Mechanistically, pMARCKS (phosphorylated form of MARCKS) was found to function as an E2F-1 cofactor to regulate SKP2 transcription. pMARCKS promoted cell-cycle progression by facilitating SKP2 expression, suppressing p27(Kip1) and potentially counteracting drug-induced cell-cycle arrest by promoting Cyclin E/CDK2 activity. Importantly, MARCKS knockdown in combination with bortezomib treatment overcame bortezomib resistance, significantly inhibited tumor growth and prolonged host survival in a MM xenograft model. These data provide a rationale for therapeutic targeting of pMARCKS to improve the outcome of patients with refractory/relapsed MM.
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