Adherence to AUA guidelines for the work-up, medical management, surgical evaluation and treatment of BPH: Work from a quality improvement collaborative.

INTRODUCTION: Previous studies noted varied adherence to clinical practice guidelines (CPGs), but studies are yet to quantify adherence to American Urological Association BPH guidelines. We studied guideline adherence in the context of a new quality improvement collaborative (QIC). METHODS: Data were collected as part of a statewide QIC. Medical records for patients undergoing select CPT codes from January 2020 to May 2022 were retrospectively reviewed for adherence to selected BPH guidelines. RESULTS: Most men were treated with transurethral resection of the prostate. Notably, 53.3% of men completed an IPSS and 52.3% had a urinalysis. 4.7% were counseled on behavioral modifications, 15.0% on medical therapy, and 100% on procedural options. For management, 79.4% were taking alpha-blockers and 59.8% were taking a 5-ARI. For evaluation, 57% had a PVR, 63.6% had prostate size measurement, 37.4% had uroflowmetry, and 12.3% were counseled about treatment failure. Postoperatively, 51.6% completed an IPSS, 57% had a PVR, 6.50% had uroflowmetry, 50.6% stopped their alpha-blocker, and 75.0% stopped their 5-ARI. CONCLUSIONS: There was adherence to preoperative testing recommendations, but patient counseling was lacking in the initial work-up and preoperative evaluation. We will convey the data to key stakeholders, expand data collection to other institutions, and devise an improvement implementation plan.

Theory of radiologist interaction with instant messaging decision support tools: A sequential-explanatory study.

Radiology specific clinical decision support systems (CDSS) and artificial intelligence are poorly integrated into the radiologist workflow. Current research and development efforts of radiology CDSS focus on 4 main interventions, based around exam centric time points-after image acquisition, intra-report support, post-report analysis, and radiology workflow adjacent. We review the literature surrounding CDSS tools in these time points, requirements for CDSS workflow augmentation, and technologies that support clinician to computer workflow augmentation. We develop a theory of radiologist-decision tool interaction using a sequential explanatory study design. The study consists of 2 phases, the first a quantitative survey and the second a qualitative interview study. The phase 1 survey identifies differences between average users and radiologist users in software interventions using the User Acceptance of Information Technology: Toward a Unified View (UTAUT) framework. Phase 2 semi-structured interviews provide narratives on why these differences are found. To build this theory, we propose a novel solution called Radibot-a conversational agent capable of engaging clinicians with CDSS as an assistant using existing instant messaging systems supporting hospital communications. This work contributes an understanding of how radiologist-users differ from the average user and can be utilized by software developers to increase satisfaction of CDSS tools within radiology.

Is There Such a Thing as a Biosignature?

The concept of a biosignature is widely used in astrobiology to suggest a link between some observation and a biological cause, given some context. The term itself has been defined and used in several ways in different parts of the scientific community involved in the search for past or present life on Earth and beyond. With the ongoing acceleration in the search for life in distant time and/or deep space, there is a need for clarity and accuracy in the formulation and reporting of claims. Here, we critically review the biosignature concept(s) and the associated nomenclature in light of several problems and ambiguities emphasized by recent works. One worry is that these terms and concepts may imply greater certainty than is usually justified by a rational interpretation of the data. A related worry is that terms such as "biosignature" may be inherently misleading, for example, because the divide between life and non-life-and their observable effects-is fuzzy. Another worry is that different parts of the multidisciplinary community may use non-equivalent or conflicting definitions and conceptions, leading to avoidable confusion. This review leads us to identify a number of pitfalls and to suggest how they can be circumvented. In general, we conclude that astrobiologists should exercise particular caution in deciding whether and how to use the concept of biosignature when thinking and communicating about habitability or life. Concepts and terms should be selected carefully and defined explicitly where appropriate. This would improve clarity and accuracy in the formulation of claims and subsequent technical and public communication about some of the most profound and important questions in science and society. With this objective in mind, we provide a checklist of questions that scientists and other interested parties should ask when assessing any reported detection of a "biosignature" to better understand exactly what is being claimed.

Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons.

Proper cortical lamination is essential for cognition, learning, and memory. Within the somatosensory cortex, pyramidal excitatory neurons elaborate axon collateral branches in a laminar-specific manner that dictates synaptic partners and overall circuit organization. Here, we leverage both male and female mouse models, single-cell labeling and imaging approaches to identify intrinsic regulators of laminar-specific collateral, also termed interstitial, axon branching. We developed new approaches for the robust, sparse, labeling of Layer II/III pyramidal neurons to obtain single-cell quantitative assessment of axon branch morphologies. We combined these approaches with cell-autonomous loss-of-function (LOF) and overexpression (OE) manipulations in an in vivo candidate screen to identify regulators of cortical neuron axon branch lamination. We identify a role for the cytoskeletal binding protein drebrin (Dbn1) in regulating Layer II/III cortical projection neuron (CPN) collateral axon branching in vitro LOF experiments show that Dbn1 is necessary to suppress the elongation of Layer II/III CPN collateral axon branches within Layer IV, where axon branching by Layer II/III CPNs is normally absent. Conversely, Dbn1 OE produces excess short axonal protrusions reminiscent of nascent axon collaterals that fail to elongate. Structure-function analyses implicate Dbn1S142 phosphorylation and Dbn1 protein domains known to mediate F-actin bundling and microtubule (MT) coupling as necessary for collateral branch initiation upon Dbn1 OE. Taken together, these results contribute to our understanding of the molecular mechanisms that regulate collateral axon branching in excitatory CPNs, a key process in the elaboration of neocortical circuit formation.SIGNIFICANCE STATEMENT Laminar-specific axon targeting is essential for cortical circuit formation. Here, we show that the cytoskeletal protein drebrin (Dbn1) regulates excitatory Layer II/III cortical projection neuron (CPN) collateral axon branching, lending insight into the molecular mechanisms that underlie neocortical laminar-specific innervation. To identify branching patterns of single cortical neurons in vivo, we have developed tools that allow us to obtain detailed images of individual CPN morphologies throughout postnatal development and to manipulate gene expression in these same neurons. Our results showing that Dbn1 regulates CPN interstitial axon branching both in vivo and in vitro may aid in our understanding of how aberrant cortical neuron morphology contributes to dysfunctions observed in autism spectrum disorder and epilepsy.

Ability of artificial intelligence to identify self-reported race in chest x-ray using pixel intensity counts.

Purpose: Prior studies show convolutional neural networks predicting self-reported race using x-rays of chest, hand and spine, chest computed tomography, and mammogram. We seek an understanding of the mechanism that reveals race within x-ray images, investigating the possibility that race is not predicted using the physical structure in x-ray images but is embedded in the grayscale pixel intensities. Approach: Retrospective full year 2021, 298,827 AP/PA chest x-ray images from 3 academic health centers across the United States and MIMIC-CXR, labeled by self-reported race, were used in this study. The image structure is removed by summing the number of each grayscale value and scaling to percent per image (PPI). The resulting data are tested using multivariate analysis of variance (MANOVA) with Bonferroni multiple-comparison adjustment and class-balanced MANOVA. Machine learning (ML) feed-forward networks (FFN) and decision trees were built to predict race (binary Black or White and binary Black or other) using only grayscale value counts. Stratified analysis by body mass index, age, sex, gender, patient type, make/model of scanner, exposure, and kilovoltage peak setting was run to study the impact of these factors on race prediction following the same methodology. Results: MANOVA rejects the null hypothesis that classes are the same with 95% confidence (F 7.38, P<0.0001) and balanced MANOVA (F 2.02, P<0.0001). The best FFN performance is limited [area under the receiver operating characteristic (AUROC) of 69.18%]. Gradient boosted trees predict self-reported race using grayscale PPI (AUROC 77.24%). Conclusions: Within chest x-rays, pixel intensity value counts alone are statistically significant indicators and enough for ML classification tasks of patient self-reported race.

Robot-assisted laparoscopic removal of an extraperitoneal pelvic solitary fibrous tumor.

•Pelvic SFTs are rare, typically benign soft tissue neoplasms that pose a diagnostic challenge for gynecologists.•Retroperitoneal pelvic SFTs can mimic gynecologic malignancies and should be considered in diagnosis of a solitary pelvic mass.•Pathologic diagnosis is typically confirmed by immunohistochemistry staining positively for CD34 and STAT6.•Complete surgical excision is recommended for these tumors and can be completed with a minimally invasive approach.•Close long-term follow-up is necessary due to possible recurrence or metastasis, especially for high-risk pathologic features.

Persistence of surrogates for high consequence viral and bacterial pathogens in a pilot-scale activated sludge treatment system.

The persistence of high consequence public health pathogens in a wastewater treatment system can significantly impact worker safety, as well as the public and downstream water bodies, particularly if the system is forced to shut down the treatment processes. This study utilizes organism viability to compare the persistence of three pathogen surrogates in wastewater using a pilot-scale activated sludge treatment (AST) system, operated to mimic treatment processes of large-scale plants. Bacillus globigii spores, surrogate for Bacillus anthracis, persisted in the AST system for at least a 50-day observation period leading to a possible steady condition far beyond the solid retention time for sludge particles. MS2 bacteriophage, surrogate for Poliovirus and other non-enveloped enteric viruses, was observed for up to 35 days after introduction, which largely and expectedly correlated to the measured solid retention time. Phi-6 bacteriophage, a surrogate for Ebola virus and other enveloped viruses, was detected for no more than 4 days after introduction, even though the AST system was operated to provide three times slower solids removal than for the other surrogates. This suggests Phi-6 is subject to inactivation under AST conditions rather than physical removal. These results may suggest similar persistence for the surrogated pathogens, leading to appropriate consequence management actions.

Atmospheric characterization of terrestrial exoplanets in the mid-infrared: biosignatures, habitability, and diversity.

Exoplanet science is one of the most thriving fields of modern astrophysics. A major goal is the atmospheric characterization of dozens of small, terrestrial exoplanets in order to search for signatures in their atmospheres that indicate biological activity, assess their ability to provide conditions for life as we know it, and investigate their expected atmospheric diversity. None of the currently adopted projects or missions, from ground or in space, can address these goals. In this White Paper, submitted to ESA in response to the Voyage 2050 Call, we argue that a large space-based mission designed to detect and investigate thermal emission spectra of terrestrial exoplanets in the mid-infrared wavelength range provides unique scientific potential to address these goals and surpasses the capabilities of other approaches. While NASA might be focusing on large missions that aim to detect terrestrial planets in reflected light, ESA has the opportunity to take leadership and spearhead the development of a large mid-infrared exoplanet mission within the scope of the "Voyage 2050" long-term plan establishing Europe at the forefront of exoplanet science for decades to come. Given the ambitious science goals of such a mission, additional international partners might be interested in participating and contributing to a roadmap that, in the long run, leads to a successful implementation. A new, dedicated development program funded by ESA to help reduce development and implementation cost and further push some of the required key technologies would be a first important step in this direction. Ultimately, a large mid-infrared exoplanet imaging mission will be needed to help answer one of humankind's most fundamental questions: "How unique is our Earth?"

Influenza: epidemiology and hospital management.

Influenza is a cause of significant morbidity, mortality, economic and social disruption. Annual seasonal influenza epidemics result in 290,000-650,000 deaths worldwide, while influenza pandemics have resulted in many more - the A(H1N1) pandemic of 1918-1919 caused 20-50 million deaths. Healthcare systems struggle to effectively manage the constant threat because of the evolving nature of the virus. Since the start of 2021, there have been four events of concern related to influenza reported by the World Health Organization. To reduce the burden of disease and protect our global health security, it is essential that clinicians effectively identify and manage cases of influenza, as well as understand and collaborate with the wider public and global health systems. In particular, the rapid identification and management of novel influenza strains of concern is critical. The COVID-19 pandemic has instigated improvements in influenza preparedness guidelines and management protocols. It has accelerated healthcare innovation, with novel tools to manage respiratory disease more effectively. Innovative technologies, new pharmaceuticals and improved global surveillance are changing the way healthcare systems respond to influenza and other diseases to ensure global health resilience and effective management of future outbreaks.

Managing intensive care admissions when there are not enough beds during the COVID-19 pandemic: a systematic review.

The surge in cases of severe COVID-19 has resulted in clinicians triaging intensive care unit (ICU) admissions in places where demand has exceeded capacity. In order to assist difficult triage decisions, clinicians require clear guidelines on how to prioritise patients. Existing guidelines show significant variability in their development, interpretation, implementation and an urgent need for a robust synthesis of published guidance. To understand how to manage which patients are admitted to ICU, and receive mechanical ventilatory support, during periods of high demand during the COVID-19 pandemic, a systematic review was performed. Databases of indexed literature (Medline, Embase, Web of Science, and Global Health) and grey literature (Google.com and MedRxiv), published from 1 January until 2 April 2020, were searched. Search terms included synonyms of COVID-19, ICU, ventilation, and triage. Only formal written guidelines were included. There were no exclusion criteria based on geographical location or publication language. Quality appraisal of the guidelines was performed using the Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and the Appraisal of Guidelines for Research and Evaluation Instrument Recommendation EXcellence (AGREE REX) appraisal tools, and key themes related to triage were extracted using narrative synthesis. Of 1902 unique records identified, nine relevant guidelines were included. Six guidelines were national or transnational level guidance (UK, Switzerland, Belgium, Australia and New Zealand, Italy, and Sri Lanka), with one state level (Kansas, USA), one international (Extracorporeal Life Support Organization) and one specific to military hospitals (Department of Defense, USA). The guidelines covered several broad themes: use of ethical frameworks, criteria for ICU admission and discharge, adaptation of criteria as demand changes, equality across health conditions and healthcare systems, decision-making processes, communication of decisions, and guideline development processes. We have synthesised the current guidelines and identified the different approaches taken globally to manage the triage of intensive care resources during the COVID-19 pandemic. There is limited consensus on how to allocate the finite resource of ICU beds and ventilators, and a lack of high-quality evidence and guidelines on resource allocation during the pandemic. We have developed a set of factors to consider when developing guidelines for managing intensive care admissions, and outlined implications for clinical leads and local implementation.

Atmospheric Nitrogen When Life Evolved on Earth.

The amount of nitrogen (N2) present in the atmosphere when life evolved on our planet is central for understanding the production of prebiotic molecules and, hence, is a fundamental quantity to constrain. Estimates of atmospheric molecular nitrogen partial surface pressures during the Archean, however, widely vary in the literature. In this study, we apply a model that combines newly gained insights into atmospheric escape, magma ocean duration, and outgassing evolution. Results suggest <420 mbar surface molecular nitrogen at the time when life originated, which is much lower compared with estimates in previous works and hence could impact our understanding of the production rate of prebiotic molecules such as hydrogen cyanide. Our revised values provide new input for atmospheric chamber experiments that simulate prebiotic chemistry on the early Earth. Our results that assume negligible nitrogen escape rates are in agreement with research based on solidified gas bubbles and the oxidation of iron in micrometeorites at 2.7 Gyr ago, which suggest that the atmospheric pressure was probably less than half the present-day value. Our results contradict previous studies that assume N2 partial surface pressures during the Archean were higher than those observed today and suggest that, if the N2 partial pressure were low in the Archean, it would likely be low in the Hadean as well. Furthermore, our results imply a biogenic nitrogen fixation rate from 9 to 14 Teragram N2 per year (Tg N2/year), which is consistent with modern marine biofixation rates and, hence, indicate an oceanic origin of this fixation process.

Kidney Allograft Recipients Diagnosed with Coronavirus Disease-2019: A Single Center Report

BackgroundOrgan graft recipients receiving immunosuppressive therapy are likely to be at heightened risk for the Coronavirus Disease 2019 (Covid-19) and adverse outcomes including death. It is therefore important to characterize the clinical course and outcome of Covid-19 in this vulnerable population and identify therapeutic strategies that are safe. MethodsWe performed a retrospective chart review of 54 adult kidney transplant patients diagnosed with Covid-19 and all managed in New York State, the epicenter of Covid-19 pandemic. All 54 patients were evaluated by video visits, or phone interviews, and referred to our Fever Clinic or Emergency Room for respiratory illness symptoms consistent with Covid-19 and admitted if deemed necessary from March 13, 2020 to April 20, 2020. Characteristics of the patients were stratified by hospitalization status and disease severity. Clinical course including alterations in immunosuppressive therapy were retrieved from their electronic medical records. Primary outcomes included recovery from Covid-19 symptoms, acute kidney injury, graft failure, and case fatality rate. ResultsOf the 54 SARS-Cov-2 positive kidney transplant recipients, 39 with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. Hospitalized patients compared to non-hospitalized patients were more likely to be male, of Hispanic ethnicity, and to have cardiovascular disease. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs. 40%). In addition, 50% of hospitalized patients were treated for concurrent bacterial infections including pneumonia, urinary tract infections and sepsis. Hydroxychloroquine was prescribed in 79% of hospitalized patients and only one of 15 non-hospitalized patients. Acute kidney injury occurred in 51% of hospitalized patients. Patients with severe disease were more likely to have elevations in inflammatory biomarkers at presentation. At a median of 21 days follow up, 67% of patients have had their symptoms resolved or improved and 33% have persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired. ConclusionsClinical presentation of Covid-19 in kidney transplant recipients was similar to what has been described in the general population. The case fatality rate in our entire cohort of 54 kidney transplant recipients was reassuringly low and patients with mild symptomology could be successfully managed at home. Data from the our study suggest that a strategy of systematic screening and triage to outpatient or inpatient care, close monitoring, early management of concurrent bacterial infections and judicious use of immunosuppressive drugs rather than cessation is beneficial.

The Role of N2 as a Geo-Biosignature for the Detection and Characterization of Earth-like Habitats.

Since the Archean, N2 has been a major atmospheric constituent in Earth's atmosphere. Nitrogen is an essential element in the building blocks of life; therefore, the geobiological nitrogen cycle is a fundamental factor in the long-term evolution of both Earth and Earth-like exoplanets. We discuss the development of Earth's N2 atmosphere since the planet's formation and its relation with the geobiological cycle. Then we suggest atmospheric evolution scenarios and their possible interaction with life-forms: first for a stagnant-lid anoxic world, second for a tectonically active anoxic world, and third for an oxidized tectonically active world. Furthermore, we discuss a possible demise of present Earth's biosphere and its effects on the atmosphere. Since life-forms are the most efficient means for recycling deposited nitrogen back into the atmosphere at present, they sustain its surface partial pressure at high levels. Also, the simultaneous presence of significant N2 and O2 is chemically incompatible in an atmosphere over geological timescales. Thus, we argue that an N2-dominated atmosphere in combination with O2 on Earth-like planets within circumstellar habitable zones can be considered as a geo-biosignature. Terrestrial planets with such atmospheres will have an operating tectonic regime connected with an aerobic biosphere, whereas other scenarios in most cases end up with a CO2-dominated atmosphere. We conclude with implications for the search for life on Earth-like exoplanets inside the habitable zones of M to K stars.

Use of a trans-tracheal rapid insufflation of oxygen device in a “cannot intubate, cannot oxygenate” scenario in a parturient: a case report / 대한마취과학회지

BACKGROUND@#The trans-tracheal rapid insufflation of oxygen (TRIO) device is less commonly used and is an alternative to trans-tracheal jet ventilation for maintaining oxygenation in a “cannot intubate, cannot oxygenate” (CICO) scenario.CASE: We report the successful use of this device to maintain oxygenation after jet ventilator failure in a parturient who presented with the CICO scenario during the procedure for excision of laryngeal papilloma.@*CONCLUSIONS@#A stepwise approach to the airway plan and preparation for an event of failure is essential for good materno-fetal outcomes. The TRIO device may result in inadequate ventilation that can lead to hypercarbia and respiratory acidosis. Hence, it should only be used as a temporizing measure before a definitive airway can be secured.

Use of a trans-tracheal rapid insufflation of oxygen device in a “cannot intubate, cannot oxygenate” scenario in a parturient: a case report / 대한마취과학회지

BACKGROUND: The trans-tracheal rapid insufflation of oxygen (TRIO) device is less commonly used and is an alternative to trans-tracheal jet ventilation for maintaining oxygenation in a “cannot intubate, cannot oxygenate” (CICO) scenario. CASE: We report the successful use of this device to maintain oxygenation after jet ventilator failure in a parturient who presented with the CICO scenario during the procedure for excision of laryngeal papilloma. CONCLUSIONS: A stepwise approach to the airway plan and preparation for an event of failure is essential for good materno-fetal outcomes. The TRIO device may result in inadequate ventilation that can lead to hypercarbia and respiratory acidosis. Hence, it should only be used as a temporizing measure before a definitive airway can be secured.

Exoplanet Biosignatures: Observational Prospects.

Exoplanet hunting efforts have revealed the prevalence of exotic worlds with diverse properties, including Earth-sized bodies, which has fueled our endeavor to search for life beyond the Solar System. Accumulating experiences in astrophysical, chemical, and climatological characterization of uninhabitable planets are paving the way to characterization of potentially habitable planets. In this paper, we review our possibilities and limitations in characterizing temperate terrestrial planets with future observational capabilities through the 2030s and beyond, as a basis of a broad range of discussions on how to advance "astrobiology" with exoplanets. We discuss the observability of not only the proposed biosignature candidates themselves but also of more general planetary properties that provide circumstantial evidence, since the evaluation of any biosignature candidate relies on its context. Characterization of temperate Earth-sized planets in the coming years will focus on those around nearby late-type stars. The James Webb Space Telescope (JWST) and later 30-meter-class ground-based telescopes will empower their chemical investigations. Spectroscopic studies of potentially habitable planets around solar-type stars will likely require a designated spacecraft mission for direct imaging, leveraging technologies that are already being developed and tested as part of the Wide Field InfraRed Survey Telescope (WFIRST) mission. Successful initial characterization of a few nearby targets will be an important touchstone toward a more detailed scrutiny and a larger survey that are envisioned beyond 2030. The broad outlook this paper presents may help develop new observational techniques to detect relevant features as well as frameworks to diagnose planets based on the observables. Key Words: Exoplanets-Biosignatures-Characterization-Planetary atmospheres-Planetary surfaces. Astrobiology 18, 739-778.

Exoplanet Biosignatures: A Review of Remotely Detectable Signs of Life.

In the coming years and decades, advanced space- and ground-based observatories will allow an unprecedented opportunity to probe the atmospheres and surfaces of potentially habitable exoplanets for signatures of life. Life on Earth, through its gaseous products and reflectance and scattering properties, has left its fingerprint on the spectrum of our planet. Aided by the universality of the laws of physics and chemistry, we turn to Earth's biosphere, both in the present and through geologic time, for analog signatures that will aid in the search for life elsewhere. Considering the insights gained from modern and ancient Earth, and the broader array of hypothetical exoplanet possibilities, we have compiled a comprehensive overview of our current understanding of potential exoplanet biosignatures, including gaseous, surface, and temporal biosignatures. We additionally survey biogenic spectral features that are well known in the specialist literature but have not yet been robustly vetted in the context of exoplanet biosignatures. We briefly review advances in assessing biosignature plausibility, including novel methods for determining chemical disequilibrium from remotely obtainable data and assessment tools for determining the minimum biomass required to maintain short-lived biogenic gases as atmospheric signatures. We focus particularly on advances made since the seminal review by Des Marais et al. The purpose of this work is not to propose new biosignature strategies, a goal left to companion articles in this series, but to review the current literature, draw meaningful connections between seemingly disparate areas, and clear the way for a path forward. Key Words: Exoplanets-Biosignatures-Habitability markers-Photosynthesis-Planetary surfaces-Atmospheres-Spectroscopy-Cryptic biospheres-False positives. Astrobiology 18, 663-708.

Effects of histone methyltransferase inhibition in endometriosis.

Although the histone methyltransferase EZH2 and its product H3K27me3 are well studied in cancer, little is known about their role and potential as therapeutic targets in endometriosis. We have previously reported that endometriotic lesions are characterized by global enrichment of H3K27me3. Therefore, we aimed to (1) characterize the expression levels of EZH2 in endometriotic tissues; (2) assess H3K27me3 enrichment in candidate genes promoter regions; and (3) determine if pharmacological inhibition of EZH2 impacts migration, proliferation, and invasion of endometriotic cells. Immunohistochemistry of an endometriosis-focused tissue microarray was used to assess the EZH2 protein levels in tissues. Chromatin immunoprecipitation-qPCR was conducted to assess enrichment of H3K27me3 in candidate gene promoter regions in tissues. Immunofluorescence was performed to assess the effect of an EZH2-specific pharmacological inhibitor on H3K27me3 global enrichment in cell lines. To measure effects of the inhibitor in migration, proliferation, and invasion in vitro we used Scratch, BrdU, and Matrigel assays, respectively. Endometriotic lesions had significantly higher EZH2α nuclear immunostaining levels compared to eutopic endometrium from patients (glands, stroma) and controls (glands). H3K27me3 was enriched within promoter regions of candidate genes in some but not all of the endometriotic lesions. Inhibition of EZH2 reduced H3K27me3 levels in the endometriotic cells specifically, and also reduced migration, proliferation but not invasion of endometriotic epithelial cells (12Z). These findings support future preclinical studies to determine in vivo efficacy of EZH2 inhibitors as promising nonhormonal treatments for endometriosis, still an incurable gynecological disease.

The Effect of Varying Atmospheric Pressure upon Habitability and Biosignatures of Earth-like Planets.

Understanding the possible climatic conditions on rocky extrasolar planets, and thereby their potential habitability, is one of the major subjects of exoplanet research. Determining how the climate, as well as potential atmospheric biosignatures, changes under different conditions is a key aspect when studying Earth-like exoplanets. One important property is the atmospheric mass, hence pressure and its influence on the climatic conditions. Therefore, the aim of the present study is to understand the influence of atmospheric mass on climate, hence habitability, and the spectral appearance of planets with Earth-like, that is, N2-O2 dominated, atmospheres orbiting the Sun at 1 AU. This work utilizes a 1D coupled, cloud-free, climate-photochemical atmospheric column model; varies atmospheric surface pressure from 0.5 to 30 bar; and investigates temperature and key species profiles, as well as emission and brightness temperature spectra in a range between 2 and 20 µm. Increasing the surface pressure up to 4 bar leads to an increase in the surface temperature due to increased greenhouse warming. Above this point, Rayleigh scattering dominates, and the surface temperature decreases, reaching surface temperatures below 273 K (approximately at ∼34 bar surface pressure). For ozone, nitrous oxide, water, methane, and carbon dioxide, the spectral response either increases with surface temperature or pressure depending on the species. Masking effects occur, for example, for the bands of the biosignatures ozone and nitrous oxide by carbon dioxide, which could be visible in low carbon dioxide atmospheres. Key Words: Planetary habitability and biosignatures-Atmospheres-Radiative transfer. Astrobiology 18, 116-132.

Influenza and other emerging respiratory viruses.

Acute respiratory infections are one of the top five causes of mortality worldwide and contribute to >4 million deaths per year. Consequently, emerging respiratory viruses are a continuing threat to global health security and have the potential to affect our economies. Since the millennium, there have been around a dozen different outbreaks, several capturing international interest. The outbreak of severe acute respiratory syndrome coronavirus saw the beginning of an extensive global collaboration and has influenced many outbreak preparedness protocols now in place. Avian influenza is a particular threat, with cases of A(H5N1) and A(H7N9) reported most recently. Middle East respiratory syndrome coronavirus is causing continuing concerns with outbreaks in the Arabian Peninsula. Healthcare facilities worldwide play a crucial role in identifying threats and must be vigilant. Particularly important is identifying and managing emerging respiratory viruses when they are infrequently encountered. Surveillance, continuing research, vaccine and treatment developments are key to guiding the efforts and actions of healthcare workers, international health organizations, governments and other stakeholders. Each individual has a part to play in protecting our global health.