Acanthamoeba Encephalitis in Patient with Systemic Lupus, India

We report a fatal case of encephalitis caused by Acanthamoeba in a 24-year-old woman from India with systemic lupus erythematosus. Diagnosis was made by identification of amebas in brain sections by immunofluorescence analysis and confirmed by demonstrating Acanthamoeba mitochondrial 16S rRNA gene DNA in brain tissue sections

A Comparison of Near Simultaneous Lidar Returns and Particulate Collections on Filters Flown at Six Stratospheric Altitudes

Collections of particulates on both Los Alamos Scientific Laboratory (LASL) and National Center for Atmospheric Research (NCAR) filter systems were made from an RB 57F aircraft flown at one tropospheric and six stratospheric altitudes over the Boulder, Colorado, area. This daytime flight was spanned by lidar returns on evenings before and after the flight. Scanning electron microscope examination of the LASL filters showed no evidence of solid particulates greater than 2 micrometers (the instrumental resolving power). Quantitative analysis of the NCAR filters yielded chemical composition and mass. The mass values were normalized to the total air flow through the filters to yield mass mixing ratios at the various altitudes. The lidar returns, normalized to molecular densities obtained from sonde data, were put in the form of particulate scattering divided by molecular scattering, i. e., an optical mixing ratio. A plot of the optical mixing ratio versus mass mixing ratio, in the stratosphere, yielded linear relationship, for five of the six data points, going through the origin

Offshore Radiation Observations for Climate Research at the CERES Ocean Validation Experiment

When radiometers on a satellite are pointed towards the planet with the goal of understanding a phenomenon quantitatively, rather than just creating a pleasing image, the task at hand is often problematic. The signal at the detector can be affected by scattering, absorption, and emission; and these can be due to atmospheric constituents (gases, clouds, and aerosols), the earth's surface, and subsurface features. When targeting surface phenomena, the remote sensing algorithm needs to account for the radiation associated with the atmospheric constituents. Likewise, one needs to correct for the radiation leaving the surface, when atmospheric phenomena are of interest. Rigorous validation of such remote sensing products is a real challenge. In visible and near infrared wavelengths, the jumble of effects on atmospheric radiation are best accomplished over dark surfaces with fairly uniform reflective properties (spatial homogeneity) in the satellite instrument's field of view (FOV). The ocean's surface meets this criteria; land surfaces - which are brighter, more spatially inhomogeneous, and more changeable with time - generally do not. NASA's Clouds and the Earth's Radiant Energy System (CERES) project has used this backdrop to establish a radiation monitoring site in Virginia's coastal Atlantic Ocean. The project, called the CERES Ocean Validation Experiment (COVE), is located on a rigid ocean platform allowing the accurate measurement of radiation parameters that require precise leveling and pointing unavailable from ships or buoys. The COVE site is an optimal location for verifying radiative transfer models and remote sensing algorithms used in climate research; because of the platform's small size, there are no island wake effects; and suites of sensors can be simultaneously trained both on the sky and directly on ocean itself. This paper describes the site, the types of measurements made, multiple years of atmospheric and ocean surface radiation observations, and satellite validation results

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. EXPERIMENTAL DESIGN: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. RESULTS: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. CONCLUSIONS: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety

Caenorhabditis elegans Semi-Automated Liquid Screen Reveals a Specialized Role for the Chemotaxis Gene cheB2 in Pseudomonas aeruginosa Virulence

Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections in a variety of animal and plant hosts. Caenorhabditis elegans is a simple model with which one can identify bacterial virulence genes. Previous studies with C. elegans have shown that depending on the growth medium, P. aeruginosa provokes different pathologies: slow or fast killing, lethal paralysis and red death. In this study, we developed a high-throughput semi-automated liquid-based assay such that an entire genome can readily be scanned for virulence genes in a short time period. We screened a 2,200-member STM mutant library generated in a cystic fibrosis airway P. aeruginosa isolate, TBCF10839. Twelve mutants were isolated each showing at least 70% attenuation in C. elegans killing. The selected mutants had insertions in regulatory genes, such as a histidine kinase sensor of two-component systems and a member of the AraC family, or in genes involved in adherence or chemotaxis. One mutant had an insertion in a cheB gene homologue, encoding a methylesterase involved in chemotaxis (CheB2). The cheB2 mutant was tested in a murine lung infection model and found to have a highly attenuated virulence. The cheB2 gene is part of the chemotactic gene cluster II, which was shown to be required for an optimal mobility in vitro. In P. aeruginosa, the main player in chemotaxis and mobility is the chemotactic gene cluster I, including cheB1. We show that, in contrast to the cheB2 mutant, a cheB1 mutant is not attenuated for virulence in C. elegans whereas in vitro motility and chemotaxis are severely impaired. We conclude that the virulence defect of the cheB2 mutant is not linked with a global motility defect but that instead the cheB2 gene is involved in a specific chemotactic response, which takes place during infection and is required for P. aeruginosa pathogenicity

Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study

<p>Abstract</p> <p>Background</p> <p>Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes.</p> <p>Methods</p> <p>A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively.</p> <p>Results</p> <p>After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m²) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (≥ 25 kg/m²). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6).</p> <p>Conclusions</p> <p>These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.</p

A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis elegans

A proper immune response ensures survival in a hostile environment and promotes longevity. Recent evidence indicates that innate immunity, beyond antimicrobial effectors, also relies on host-defensive mechanisms. The Caenorhabditis elegans transcription factor SKN-1 regulates xenobiotic and oxidative stress responses and contributes to longevity, however, its role in immune defense is unknown. Here we show that SKN-1 is required for C. elegans pathogen resistance against both Gram-negative Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis bacteria. Exposure to P. aeruginosa leads to SKN-1 accumulation in intestinal nuclei and transcriptional activation of two SKN-1 target genes, gcs-1 and gst-4. Both the Toll/IL-1 Receptor domain protein TIR-1 and the p38 MAPK PMK-1 are required for SKN-1 activation by PA14 exposure. We demonstrate an early onset of immunosenescence with a concomitant age-dependent decline in SKN-1-dependent target gene activation, and a requirement of SKN-1 to enhance pathogen resistance in response to longevity-promoting interventions, such as reduced insulin/IGF-like signaling and preconditioning H2O2 treatment. Finally, we find that wdr-23(RNAi)-mediated constitutive SKN-1 activation results in excessive transcription of target genes, confers oxidative stress tolerance, but impairs pathogen resistance. Our findings identify SKN-1 as a novel regulator of innate immunity, suggests its involvement in immunosenescence and provide an important crosstalk between pathogenic stress signaling and the xenobiotic/oxidative stress response

The Mitochondrial Genome of the Lycophyte Huperzia squarrosa: The Most Archaic Form in Vascular Plants

Mitochondrial genomes have maintained some bacterial features despite their residence within eukaryotic cells for approximately two billion years. One of these features is the frequent presence of polycistronic operons. In land plants, however, it has been shown that all sequenced vascular plant chondromes lack large polycistronic operons while bryophyte chondromes have many of them. In this study, we provide the completely sequenced mitochondrial genome of a lycophyte, from Huperzia squarrosa, which is a member of the sister group to all other vascular plants. The genome, at a size of 413,530 base pairs, contains 66 genes and 32 group II introns. In addition, it has 69 pseudogene fragments for 24 of the 40 protein- and rRNA-coding genes. It represents the most archaic form of mitochondrial genomes of all vascular plants. In particular, it has one large conserved gene cluster containing up to 10 ribosomal protein genes, which likely represents a polycistronic operon but has been disrupted and greatly reduced in the chondromes of other vascular plants. It also has the least rearranged gene order in comparison to the chondromes of other vascular plants. The genome is ancestral in vascular plants in several other aspects: the gene content resembling those of charophytes and most bryophytes, all introns being cis-spliced, a low level of RNA editing, and lack of foreign DNA of chloroplast or nuclear origin