Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2

Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2(–/–)) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2(–/–) mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2(–/–) mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension. J. Clin. Invest. 103:683–689 (1999

Movement of Walleyes in Lakes Erie and St. Clair Inferred from Tag Return and Fisheries Data

Lake Erie walleyes Sander vitreus support important fisheries and have been managed as one stock, although preliminary tag return and genetic analyses suggest the presence of multiple stocks that migrate among basins within Lake Erie and into other portions of the Great Lakes. We examined temporal and spatial movement and abundance patterns of walleye stocks in the three basins of Lake Erie and in Lake St. Clair with the use of tag return and sport and commercial catchâ perâ unit effort (CPUE) data from 1990 to 2001. Based on summer tag returns, western basin walleyes migrated to the central and eastern basins of Lake Erie and to Lake St. Clair and southern Lake Huron, while fish in the central and eastern basins of Lake Erie and in Lake St. Clair were primarily caught within the basins where they were tagged. Seasonal changes in sport and commercial effort and CPUE in Lake Erie confirmed the walleye movements suggested by tag return data. Walleyes tagged in the western basin but recaptured in the central or eastern basin of Lake Erie were generally larger (or older) than those recaptured in the western basin of Lake Erie or in Lake St. Clair. Within spawning stocks, female walleyes had wider ranges of movement than males and there was considerable variation in movement direction, minimum distance moved (mean distance between tagging sites and recapture locations), and mean length among individual spawning stocks. Summer temperatures in the western basin often exceeded the optimal temperature (20â 23°C) for growth of large walleyes, and the migration of western basin walleyes might represent a sizeâ dependent response to warm summer temperatures. Cooler temperatures and abundant softâ rayed fish probably contributed to an energetically favorable foraging habitat in the central and eastern basins that attracted large walleyes during summer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141620/1/tafs0539.pd

High-sensitivity transition-edge-sensed bolometers: improved speed and characterization with AC and DC bias

We report on efforts to improve the speed of low-G far-infrared transition-edged-sensed bolometers. We use a fabrication process that does not require any dry etch steps to reduce heat capacity on the suspended device and measure a reduction in the detector time constant. However, we also measure an increase in the temperature-normalized thermal conductance (G), and a corresponding increase in the noise-equivalent power (NEP). We employ a new near-IR photon-noise technique using a near-IR laser to calibrate the frequency-domain multiplexed AC system and compare the results to a well-understood DC circuit. We measure an NEP white noise level of 0.8 aW/rtHz with a 1/f knee below 0.1 Hz and a time constant of 3.2 ms.Comment: 27 pages, 16 figures. This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in J. Appl. Phys. 134 (9) and may be found at https://doi.org/10.1063/5.015720

Exploring the perceptions of former ICU patients and clinical staff on barriers and facilitators to the implementation of virtual reality exposure therapy: A qualitative study

Background: Virtual reality (VR) as a digital technology has developed rapidly, becoming more realistic, portable, sensory and easier to navigate. Although studies have found VR to be effective for many clinical applications, patients and clinicians have described several barriers to the successful implementation of this technology. To remove barriers for implementation of VR in health care, a greater understanding is needed of how VR can integrate into clinical environments, particularly complex settings such as an intensive care unit. Aim: This study aimed to explore the perceived barriers and facilitators for the implementation of VR exposure therapy for intensive care patients and clinical staff. Study Design: A qualitative study using an Interpretative Description approach was undertaken. Semi‐structured focus groups were conducted with 13 participants: nine patients and four health care professionals. Focus groups explored barriers and facilitators of using virtual reality (VR) exposure therapy in intensive care. Thematic analysis was employed to produce codes and themes. Results: In total, eight themes describing the perceived barriers and facilitators to implementing VR exposure therapy were identified. Four themes related to the perceived barriers of implementing VR exposure therapy in intensive care were identified: psychological, sensory, environmental and staff competency and confidence. There were a further four themes related to the perceived facilitators to the implementation of VR exposure therapy: staff training, patient capacity, orientation to technology and support during the intervention. Conclusions: This study identified novel barriers and facilitators that could be expected when implementing VR exposure therapy for patients' post‐intensive care unit stay. The findings suggest that psychological barriers of fear and apprehension were expected to provoke patient avoidance of exposure therapy. Perceived barriers for staff focused on preparedness to deliver the VR exposure therapy and a lack of technological competence. Both patients and staff stated that a comprehensive induction, orientation and training could facilitate VR exposure therapy, improving engagement. Relevance to Clinical Practice: This study has identified that with appropriate staff training, resources, and integration into current patient care pathways, VR exposure therapy may be a valuable intervention to support patient recovery following critical illness. Prior to undertaking VR exposure therapy, patients often need reassurance that side‐effects can be managed, and that they can easily control their virtual exposure experience

Morphologic characteristics of posterior polymorphous dystrophy. A study of nine corneas and review of the literature

Based on their own study of nine corneas with clinically documented posterior polymorphous dystrophy and a review of the literature, the authors describe the morphologic features of this entity. Study by phase contrast light microscopy and transmission and scanning electron microscopy found that changes were primarily in the endothelium and consisted of endothelial cell degeneration and loss with focal fibroblastic and epithelial-like cell transformation. Secondary alterations of Descemet's membrane were seen; they consisted of abnormal lamination with deposition of abnormal collagen material, particularly in the posterior collagen layer, and formation of guttate excrescences and pits.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24707/1/0000128.pd

The range of uses of virtual reality for intensive care unit staff training: A narrative synthesis scoping review

Background The use of virtual reality (VR) in medical education allows learners to make mistakes safely without risk to patients and to refine a range of clinical skills by repetition. However, there is still wide variability both between, and within countries regarding the amount of training delivered using VR, particularly in relation to intensive care medicine Objectives To identify the range of uses, phase of development and effectiveness of VR for intensive care unit (ICU) staff training. Methods The review followed the scoping review framework set out by Levac et al. (2010). A multi-database search was undertaken. All study types were included if they explored the use of VR for intensive care staff (ICU) staff training. Full paper screening, data extraction and assessment of bias was carried out by a single reviewer with verification by a second reviewer. A narrative synthesis was chosen to summarize the data. Results The search strategy identified 647 records. Following the removal of duplicates, screening of titles, abstracts and full texts, five studies were included. VR for ICU training has primarily focused on skill acquisition for surgical procedures. The majority of studies in this area were classified to be at an early stage of assessing acceptability, tolerability and efficacy. There was very low-quality evidence that VR for ICU training is effective. Conclusions Studies have explored the use of VR for a small number of surgical procedures and emergency patient scenarios. VR for ICU training demonstrates some potential, however further development and high-quality research is required. Research relating to virtual reality for ICU staff training is currently of weak methodological quality and as such, no recommendations to clinical practise can be made. Wherever possible when using VR for ICU staff training it should be utilized as part of a high-quality study

PATRIC, the bacterial bioinformatics database and analysis resource

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10 000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issu

Sediment undulations on the Llobregat prodelta: Signs of early slope instability or sedimentary bedforms?

A field of sediment undulations has been mapped by means of high resolution multibeam bathymetry and seismic reflection profiles in the Llobregat River prodelta, off the city of Barcelona, Catalonia, Spain. Similar features had previously been recognized in other prodelta environments and interpreted either as downslope sediment deformation or sedimentary structures induced by bottom currents or hyperpycnal flows. Since the study area is undergoing significant offshore development, proper interpretation of such sediment undulations is needed for a correct risk assessment. The occurrence of the sediment undulations is restricted to the prodelta front on slope gradients between 3 and 0.2º. The undulations have developed at the edge and atop an area of gas bearing sediments within the Late-Holocene high-stand mud wedge. An evaluation is made of the characteristics of the sediment undulations in order to determine the most likely process for the origin of these structures. Amongst these characteristics are the continuity of the reflections and lack of diffractions in between different undulations, their size distribution (large to small) both from shallow to deep and with depth in section, the asymmetry (decreasing from proximal to distal), the crest to trough vertical distance on the landward side of the undulations (up to 0.5 m), and the lack of features that could indicate a progressive movement such as growth structures and drag folds. These characteristics indicate that the sediment undulations on the Llobregat River prodelta do not result from sediment deformation, but rather from the interaction of bottom currents generated by hyperpycnal flows from the Llobregat River with regional sea water circulation. Their identification as sediment waves implies that such features do not pose a major hazard for urther offshore development