Search

The primary objectives of any high-volume surgery department should be patient safety, block time utilization and operating room efficiency. Reducing preparation time in the OR prior to actual surgery can improve operating room efficiency and utilization, but only if patient safety can be maintained. With this goal, this study evaluated a novel skin preparation technique using a device named ULTRAPREP™, a sterile, medical-grade plastic bag that is applied to the upper or lower extremity in the pre-operative holding area which allows for skin disinfection outside the OR (referred to as "disinfection bag"). The study compared preparation times required in the OR and antiseptic efficiency (through Colony Forming Units (CFU) counts) for traditional methods versus using the disinfection bag on a total of 115 patients undergoing podiatric or orthopedic surgeries (upper and lower extremities) in one hospital. The disinfection bag reduced skin preparation time in the OR from 16.8±3.5min to 10.9±2.7min, which was a 35.2% reduction, and was statistically significant (p<0.01). Skin antisepsis met safety standards of <15 CFUs for all cases regardless of preparation type at 48h and 72h. There was no statistical difference in CFU levels between the traditional and disinfection bag methods at 48h or 72h (p>0.11). Therefore, ULTRAPREP™ has shown the ability to decrease operating room time while keeping surgical site infection rates to a minimum. Minimizing activities in the OR optimizes use of this costly resource and brings overall savings to the surgery department.

Poly(ADP-ribosylation) (PARylation) is a post-translational modification mediated by a subset of ADP-ribosyl transferases (ARTs). Although PARylation-inhibition based therapies are considered as an avenue to combat debilitating diseases such as cancer and myopathies, the role of this modification in physiological processes such as cell differentiation remains unclear. Here, we show that Tankyrase1 (TNKS1), a PARylating ART, plays a major role in myogenesis, a vital process known to drive muscle fiber formation and regeneration. Although all bona fide PARPs are expressed in muscle cells, experiments using siRNA-mediated knockdown or pharmacological inhibition show that TNKS1 is the enzyme responsible of catalyzing PARylation during myogenesis. Via this activity, TNKS1 controls the turnover of mRNAs encoding myogenic regulatory factors such as nucleophosmin (NPM) and myogenin. TNKS1 mediates these effects by targeting RNA-binding proteins such as Human Antigen R (HuR). HuR harbors a conserved TNKS-binding motif (TBM), the mutation of which not only prevents the association of HuR with TNKS1 and its PARylation, but also precludes HuR from regulating the turnover of NPM and myogenin mRNAs as well as from promoting myogenesis. Therefore, our data uncover a new role for TNKS1 as a key modulator of RBP-mediated post-transcriptional events required for vital processes such as myogenesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Several commercial organizations have recently launched or plan to launch constellations containing thousands of satellites. Such large constellations potentially adversely affect astronomical observations. This study formulates a set of indicators that assess the impact of light pollution from different constellations on ground-based visible band astronomy. These include the statistically expected number of visible and sunlit satellites above ground-based observers, as well as the number that are also expected to be brighter than the currently recommended limit for constellation satellites. The latter indicator provides a consolidated means to evaluate the potential for a constellation to affect ground-based astronomy too severely, by simultaneously accounting for the effects of constellation population, orbital distribution as well as brightness magnitude and variability. For existing constellations, the evaluation process incorporates actual satellite photometric brightness measurements, which are becoming increasingly available in web-accessible databases and repositories. For proposed constellations, a semi-empirical method allows rough approximations of pre-launch light pollution levels, based on observed brightness distributions observed of currently orbiting analog satellites., Competing Interests: Conflict of interestThe author declares no conflict, nor competing interest in the creation of this work., (© The Author(s) 2022.)

Cachexia syndrome develops in patients with diseases such as cancer and sepsis and is characterized by progressive muscle wasting. While iNOS is one of the main effectors of cachexia, its mechanism of action and whether it could be targeted for therapy remains unexplored. Here, we show that iNOS knockout mice and mice treated with the clinically tested iNOS inhibitor GW274150 are protected against muscle wasting in models of both septic and cancer cachexia. We demonstrate that iNOS triggers muscle wasting by disrupting mitochondrial content, morphology, and energy production processes such as the TCA cycle and acylcarnitine transport. Notably, iNOS inhibits oxidative phosphorylation through impairment of complexes II and IV of the electron transport chain and reduces ATP production, leading to energetic stress, activation of AMPK, suppression of mTOR, and, ultimately, muscle atrophy. Importantly, all these effects were reversed by GW274150. Therefore, our data establish how iNOS induces muscle wasting under cachectic conditions and provide a proof of principle for the repurposing of iNOS inhibitors, such as GW274150 for the treatment of cachexia., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

The master posttranscriptional regulator HuR promotes muscle fiber formation in cultured muscle cells. However, its impact on muscle physiology and function in vivo is still unclear. Here, we show that muscle-specific HuR knockout (muHuR-KO) mice have high exercise endurance that is associated with enhanced oxygen consumption and carbon dioxide production. muHuR-KO mice exhibit a significant increase in the proportion of oxidative type I fibers in several skeletal muscles. HuR mediates these effects by collaborating with the mRNA decay factor KSRP to destabilize the PGC-1α mRNA. The type I fiber-enriched phenotype of muHuR-KO mice protects against cancer cachexia-induced muscle loss. Therefore, our study uncovers that under normal conditions HuR modulates muscle fiber type specification by promoting the formation of glycolytic type II fibers. We also provide a proof-of-principle that HuR expression can be targeted therapeutically in skeletal muscles to combat cancer-induced muscle wasting.

Activation of AMPK has been associated with pro-atrophic signaling in muscle. However, AMPK also has anti-inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory-driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα-induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A-769662, a specific AMPK activator. AICAR and A-769662 co-treatment was found to be synergistic, suggesting that the anti-cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation-driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Cachexia is a debilitating syndrome characterized by involuntary muscle wasting that is triggered at the late stage of many cancers. While the multifactorial nature of this syndrome and the implication of cytokines such as IL-6, IFNγ, and TNFα is well established, we still do not know how various effector pathways collaborate together to trigger muscle atrophy. Here, we show that IFNγ/TNFα promotes the phosphorylation of STAT3 on Y705 residue in the cytoplasm of muscle fibers by activating JAK kinases. Unexpectedly, this effect occurs both in vitro and in vivo independently of IL-6, which is considered as one of the main triggers of STAT3-mediated muscle wasting. pY-STAT3 forms a complex with NF-κB that is rapidly imported to the nucleus where it is recruited to the promoter of the iNos gene to activate the iNOS/NO pathway, a well-known downstream effector of IFNγ/TNFα-induced muscle loss. Together, these findings show that STAT3 and NF-κB respond to the same upstream signal and cooperate to promote the expression of pro-cachectic genes, the identification of which could provide effective targets to combat this deadly syndrome., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)

The deterioration of skeletal muscle that develops slowly with age, termed sarcopenia, often leads to disability and mortality in the elderly population. As the proportion of elderly citizens continues to increase due to the dramatic rise in life expectancy, there are rising concerns about the healthcare cost and social burden of caring for geriatric patients. Thus, there is a growing need to understand the underlying mechanisms of sarcopenic muscle loss so that more efficacious therapies may be developed. Building evidence suggests that the onset of age-related muscle loss is linked to the age-related changes in gene expression that occur during sarcopenia. In recent work, the posttranscriptional regulation of gene expression by RNA-binding proteins (RBPs) and microRNA (miRNA) involved in the turnover and translation of mRNA were shown as key players believed to be involved in the induction of muscle wasting. Furthermore, posttranscriptional regulation may also be linked to the reduced ability of muscle satellite cells to contribute to muscle mass during ageing, a key contributing factor to sarcopenic progression. Here we highlight how the activation of pathways such as the p38 MAPK and the phosphoinositide 3-kinase (PI3K) pathways alter the ability of RBPs to regulate the expression of their target mRNAs encoding proteins involved in cell cycle (p21 and p16), as well as myogenesis (Pax7, myogenin and MyoD). Further investigation into the role of RBPs and miRNA during sarcopenia may provide new insights into the development and progression of this disorder, which may lead to the development of new treatment options for elderly patients suffering from sarcopenia., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cachexia, or muscle-wasting syndrome, is one of the major causes of death in patients affected by diseases such as cancer, AIDS and sepsis. However, no effective anti-cachectic treatment is currently available. Here we show that a low dose of pateamine A, an inhibitor of translation initiation, prevents muscle wasting caused by the cytokines interferon γ and tumour necrosis factor α or by C26-adenocarcinoma tumours. Surprisingly, although high doses of pateamine A abrogate general translation, low doses selectively inhibit the expression of pro-cachectic factors such as inducible nitric oxide synthase. This selectivity depends on the 5'UTR of inducible nitric oxide synthase messenger RNA (mRNA) that, unlike the 5'UTR of MyoD mRNA, promotes the recruitment of inducible nitric oxide synthase mRNA to stress granules, where its translation is repressed. Collectively, our data provide a proof of principle that nontoxic doses of compounds such as pateamine A could be used as novel drugs to combat cachexia-induced muscle wasting.

Muscle atrophy-also known as muscle wasting-is a debilitating syndrome that slowly develops with age (sarcopenia) or rapidly appears at the late stages of deadly diseases such as cancer, AIDS, and sepsis (cachexia). Despite the prevalence and the drastic detrimental effects of these two syndromes, there are currently no widely used, effective treatment options for those suffering from muscle wasting. In an attempt to identify potential therapeutic targets, the molecular mechanisms of sarcopenia and cachexia have begun to be elucidated. Growing evidence suggests that inflammatory cytokines may play an important role in the pathology of both syndromes. As one of the key cytokines involved in both sarcopenic and cachectic muscle wasting, tumor necrosis factor α (TNFα) and its downstream effectors provide an enticing target for pharmacological intervention. However, to date, no drugs targeting the TNFα signaling pathway have been successful as a remedial option for the treatment of muscle wasting. Thus, there is a need to identify new effectors in this important pathway that might prove to be more efficacious targets. Inducible nitric oxide synthase (iNOS) has recently been shown to be an important mediator of TNFα-induced cachectic muscle loss, and studies suggest that it may also play a role in sarcopenia. In addition, investigations into the mechanism of iNOS-mediated muscle loss have begun to reveal potential therapeutic strategies. In this review, we will highlight the potential for targeting the iNOS/NO pathway in the treatment of muscle loss and discuss its functional relevance in sarcopenia and cachexia.

The current essay discusses the narratives of five community psychologists from the perspective of a career "calling." Each of the essays highlight different components of a calling: employing deep discernment to know the right path for oneself; experiencing a calling to do one's work, an invitation to which we choose to respond; serving community; discovering your quintessential self or "genius"; and using your gifts for the common good. Moreover, the author discusses how the essays not only illustrate calling, but also the emergence of confidence and the subjective career.

Stellar occultations--the passing of a relatively nearby body in front of a background star--can be used to probe the atmosphere of the closer body with a spatial resolution of a few kilometres (ref. 1). Such observations can yield the scale height, temperature profile, and other information about the structure of the occulting atmosphere. Occultation data acquired for Pluto's atmosphere in 1988 revealed a nearly isothermal atmosphere above a radius of approximately 1,215 km. Below this level, the data could be interpreted as indicating either an extinction layer or the onset of a large thermal gradient, calling into question the fundamental structure of this atmosphere. Another question is to what extent Pluto's atmosphere might be collapsing as it recedes from the Sun (passing perihelion in 1989 in its 248-year orbital period), owing to the extreme sensitivity of the equilibrium surface pressure to the surface temperature. Here we report observations at a variety of visible and infrared wavelengths of an occultation of a star by Pluto in August 2002. These data reveal evidence for extinction in Pluto's atmosphere and show that it has indeed changed, having expanded rather than collapsed, since 1988.

Just before earth passed through Saturn's ring plane on 10 August 1995, the Hubble Space Telescope Faint Object Spectrograph detected ultraviolet fluorescent emissions from a tenuous atmosphere of OH molecules enveloping the rings. Brightnesses decrease with increasing distance above the rings, implying a scale height of about 0.45 Saturn radii (Rs). A spatial scan 0.28Rs above the A and B rings indicates OH column densities of about 10(13) cm(-2) and number densities of up to 700 cm(-3). Saturn's rings must produce roughly 10(25) to 10(29) OH molecules per second to maintain the observed OH distribution.

The Extreme Ultraviolet Explorer (EUVE) satellite conducted extensive observations of the jovian system before, during, and after the impact of the fragments of comet Shoemaker-Levy 9 in July 1994. About 2 to 4 hours after the impacts of several of the larger fragments, the brightness of the neutral helium (He I) resonance line at 58.4 nanometers temporarily increased by a factor of about 10. The transient 58.4-nanometer brightenings are most simply explained by resonant scattering of sunlight from the widespread high-altitude remnants of the larger impact plumes. Other possible sources of emission, such as electron impact excitation of He or radiative recombination of He(+), may contribute to the observed signal.

Spectroscopic and imaging observations of the Io plasma torus were made in June and July 1994 in conjunction with the encounter of periodic comet Shoemaker-Levy 9 with Jupiter. Characteristic emissions from sulfur and oxygen ions showed a decline of about 30 percent in the extreme ultraviolet and an increase of about 40 percent in the far ultraviolet relative to preimpact observations. Changes in the extreme ultraviolet may be indicative of small changes in the torus electron temperature as a result of quenching of electrons by dust associated with the comet passage. However, no new emission features indicative of fragment dust within the torus were detected. The characteristic torus morphology seen in ground-based imaging was typical of that observed in the past.

Europa, the second large satellite out from Jupiter, is roughly the size of Earth's Moon, but unlike the Moon, it has water ice on its surface. There have been suggestions that an oxygen atmosphere should accumulate around such a body, through reactions which break up the water molecules and form molecular hydrogen and oxygen. The lighter H2 molecules would escape from Europa relatively easily, leaving behind an atmosphere rich in oxygen. Here we report the detection of atomic oxygen emission from Europa, which we interpret as being produced by the simultaneous dissociation and excitation of atmospheric O2 by electrons from Jupiter's magnetosphere. Europa's molecular oxygen atmosphere is very tenuous, with a surface pressure about 10(-11) that of the Earth's atmosphere at sea level.

Results from the occultation of the sun by Neptune imply a temperature of 750 +/- 150 kelvins in the upper levels of the atmosphere (composed mostly of atomic and molecular hydrogen) and define the distributions of methane, acetylene, and ethane at lower levels. The ultraviolet spectrum of the sunlit atmosphere of Neptune resembles the spectra of the Jupiter, Saturn, and Uranus atmospheres in that it is dominated by the emissions of H Lyman alpha (340 +/- 20 rayleighs) and molecular hydrogen. The extreme ultraviolet emissions in the range from 800 to 1100 angstroms at the four planets visited by Voyager scale approximately as the inverse square of their heliocentric distances. Weak auroral emissions have been tentatively identified on the night side of Neptune. Airglow and occultation observations of Triton's atmosphere show that it is composed mainly of molecular nitrogen, with a trace of methane near the surface. The temperature of Triton's upper atmosphere is 95 +/- 5 kelvins, and the surface pressure is roughly 14 microbars.