This biography examines the long life of the traveller and author Stephen Graham. Graham walked across large parts of the Tsarist Empire in the years before 1917, describing his adventures in a ...series of books and articles that helped to shape attitudes towards Russia in Britain and the United States. In later years he travelled widely across Europe and North America, meeting some of the best known writers of the twentieth century, including H.G.Wells and Ernest Hemingway. Graham also wrote numerous novels and biographies that won him a wide readership on both sides of the Atlantic. This book traces Graham’s career as a world traveller, and provides a rich portrait of English, Russian and American literary life in the first half of the twentieth century. It also examines how many aspects of his life and writing coincide with contemporary concerns, including the development of New Age spirituality and the rise of environmental awareness. Beyond Holy Russia is based on extensive research in archives of private papers in Britain and the USA and on the many works of Graham himself. The author describes with admirable tact and clarity Graham’s heterodox and convoluted spiritual quest. The result is a fascinating portrait of a man who was for many years a significant literary figure on both sides of the Atlantic.
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the ...past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.
Digital Technology for Diabetes. Reply Hughes, Michael S; Addala, Ananta; Buckingham, Bruce
The New England journal of medicine,
2024-Mar-07, 20240307, Volume:
390, Issue:
10
Journal Article
Introduction
Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The ...beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery.
Methods
EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference.
Results
Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46–0.87
I
2
34%,
p
= 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23–0.68,
I
2
= 0%,
p
= 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD −2.39 95% CI −4.86 to 0.08
I
2
= 0%,
p
= 0.06) or change in 6MWT distance (WMD 9.06 95% CI −35.68, 53.81
I
2
= 88%,
p
= 0.69) was observed.
Conclusions
Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Circadian rhythms are oscillations of physiology, behavior, and metabolism that have period lengths near 24 hours. In several model organisms and humans, circadian clock genes have been characterized ...and found to be transcription factors. Because of this, researchers have used microarrays to characterize global regulation of gene expression and algorithmic approaches to detect cycling. This article presents a new algorithm, JTK_CYCLE, designed to efficiently identify and characterize cycling variables in large data sets. Compared with COSOPT and the Fisher's G test, two commonly used methods for detecting cycling transcripts, JTK_CYCLE distinguishes between rhythmic and nonrhythmic transcripts more reliably and efficiently. JTK_CYCLE's increased resistance to outliers results in considerably greater sensitivity and specificity. Moreover, JTK_CYCLE accurately measures the period, phase, and amplitude of cycling transcripts, facilitating downstream analyses. Finally, JTK_CYCLE is several orders of magnitude faster than COSOPT, making it ideal for large-scale data sets. JTK_CYCLE was used to analyze legacy data sets including NIH3T3 cells, which have comparatively low amplitude oscillations. JTK_CYCLE's improved power led to the identification of a novel cluster of RNA-interacting genes whose abundance is under clear circadian regulation. These data suggest that JTK_CYCLE is an ideal tool for identifying and characterizing oscillations in genome-scale data sets.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Exposure to the metalloid arsenic is a daily occurrence because of its environmental pervasiveness. Arsenic, which is found in several different chemical forms and oxidation states, causes acute and ...chronic adverse health effects, including cancer. The metabolism of arsenic has an important role in its toxicity. The metabolism involves reduction to a trivalent state and oxidative methylation to a pentavalent state. The trivalent arsenicals, including those methylated, have more potent toxic properties than the pentavalent arsenicals. The exact mechanism of the action of arsenic is not known, but several hypotheses have been proposed. At a biochemical level, inorganic arsenic in the pentavalent state may replace phosphate in several reactions. In the trivalent state, inorganic and organic (methylated) arsenic may react with critical thiols in proteins and inhibit their activity. Regarding cancer, potential mechanisms include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion. A better understanding of the mechanism(s) of action of arsenic will make a more confident determination of the risks associated with exposure to this chemical.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In 1966, Pohl and Hawk Science 152, 647–649 (1966) published the first demonstration of dielectrophoresis of living and dead yeast cells; their paper described how the different ways in which the ...cells responded to an applied nonuniform electric field could form the basis of a cell separation method. Fifty years later, the field of dielectrophoretic (DEP) cell separation has expanded, with myriad demonstrations of its ability to sort cells on the basis of differences in electrical properties without the need for chemical labelling. As DEP separation enters its second half-century, new approaches are being found to move the technique from laboratory prototypes to functional commercial devices; to gain widespread acceptance beyond the DEP community, it will be necessary to develop ways of separating cells with throughputs, purities, and cell recovery comparable to gold-standard techniques in life sciences, such as fluorescence- and magnetically activated cell sorting. In this paper, the history of DEP separation is charted, from a description of the work leading up to the first paper, to the current dual approaches of electrode-based and electrodeless DEP separation, and the path to future acceptance outside the DEP mainstream is considered.
We used genetic parentage analysis of 6200 potential parents and 5497 juvenile offspring to evaluate the relative reproductive success of hatchery and natural steelhead (Onchorhynchus mykiss) when ...spawning in the wild between 2008 and 2011 in the Wenatchee River, Washington. Hatchery fish originating from two prior generation hatchery parents had <20% of the reproductive success of natural origin spawners. In contrast, hatchery females originating from a cross between two natural origin parents of the prior generation had equivalent or better reproductive success than natural origin females. Males originating from such a cross had reproductive success of 26-93% that of natural males. The reproductive success of hatchery females and males from crosses consisting of one natural origin fish and one hatchery origin fish was 24-54% that of natural fish. The strong influence of hatchery broodstock origin on reproductive success confirms similar results from a previous study of a different population of the same species and suggests a genetic basis for the low reproductive success of hatchery steelhead, although environmental factors cannot be entirely ruled out. In addition to broodstock origin, fish size, return time, age, and spawning location were significant predictors of reproductive success. Our results indicate that incorporating natural fish into hatchery broodstock is clearly beneficial for improving subsequent natural spawning success, even in a population that has a decades-long history of hatchery releases, as is the case in the Wenatchee River.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. ...iAs and its methylated metabolites are primarily excreted in urine within 4-5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trivalent arsenicals are more potent toxicants than pentavalent forms. Several mechanisms of action have been proposed for arsenic-induced toxicity, but a scientific consensus has not been achieved. Biomarkers of exposure may be used to quantify exposure to iAs. The most common biomarker of exposure for iAs is the measurement of total urinary arsenic. However, consumption of seafood containing high concentrations of organic arsenic can confound estimation of iAs exposure. Because these organic species are thought to be relatively nontoxic, their presence in urine may not represent increased risk. Speciation of urinary arsenic into inorganic and organic forms, and even oxidation state, gives a more definitive indication of the exposure to iAs. Questions still remain, however, as to how reliably the measurement of urinary arsenic, either total or speciated, may predict arsenic concentrations at target tissues as well as how this measurement could be used to assess chronic exposures to iAs.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Circadian clocks are coupled to metabolic oscillations through nutrient-sensing pathways. Nutrient flux into the hexosamine biosynthesis pathway triggers covalent protein modification by O-linked ...β-D-N-acetylglucosamine (O-GlcNAc). Here we show that the hexosamine/O-GlcNAc pathway modulates peripheral clock oscillation. O-GlcNAc transferase (OGT) promotes expression of BMAL1/CLOCK target genes and affects circadian oscillation of clock genes in vitro and in vivo. Both BMAL1 and CLOCK are rhythmically O-GlcNAcylated, and this protein modification stabilizes BMAL1 and CLOCK by inhibiting their ubiquitination. In vivo analysis of genetically modified mice with perturbed hepatic OGT expression shows aberrant circadian rhythms of glucose homeostasis. These results establish the counteraction between O-GlcNAcylation and ubiquitination as a key mechanism that regulates the circadian clock and suggest a crucial role for O-GlcNAc signaling in transducing nutritional signals to the core circadian timing machinery.
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► The hexosamine/O-GlcNAc pathway regulates cellular clock oscillation ► OGT promotes expression of BMAL1/CLOCK target genes in cultured cells and liver ► Rhythmic O-GlcNAcylation stabilizes BMAL1 and CLOCK by inhibiting their ubiquitination ► Hepatic manipulation of OGT perturbs the diurnal rhythm of glucose homeostasis
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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