dan Michael Jordan's first Air Jordans up for auction at Sotheby's By feeds.reuters.com Published On :: Fri, 08 May 2020 20:37:32 -0400 An autographed and well-worn pair of basketball legend Michael Jordan's Nike shoes hits the auction block at Sotheby's on Friday, in a celebrity-infused test of the market for sneakers as highly-prized collectibles. Full Article sportsNews
dan Michael Jordan's first Air Jordans up for auction at Sotheby's By www.reuters.com Published On :: Fri, 08 May 2020 20:37:32 -0400 An autographed and well-worn pair of basketball legend Michael Jordan's Nike shoes hits the auction block at Sotheby's on Friday, in a celebrity-infused test of the market for sneakers as highly-prized collectibles. Full Article peopleNews
dan As U.S. states reopen, White House keeps CDC guidance on the shelf By www.reuters.com Published On :: Thu, 07 May 2020 20:48:20 -0400 The White House shelved a step-by-step guide prepared by U.S. health officials to help states safely reopen mass transit and businesses closed by the coronavirus pandemic, an administration official said on Thursday. This report produced by Chris Dignam. Full Article
dan The sun is too quiet, which may mean dangerous solar storms in future By www.newscientist.com Published On :: Thu, 30 Apr 2020 19:00:24 +0000 Stars that are similar to the sun in every way we can measure are mostly more active than the sun, which hints that the sun’s activity may ramp up someday, risking solar eruptions Full Article
dan Schumer: Reopening states without more tests is 'dangerous' By www.reuters.com Published On :: Thu, 07 May 2020 15:38:19 -0400 Senate Democratic Leader Chuck Schumer on Thursday said it was 'dangerous' for the Trump administration to pressure states and businesses to 'reopen without a plan for a dramatic increase in testing'. Full Article
dan As U.S. states reopen, White House keeps CDC guidance on the shelf By www.reuters.com Published On :: Thu, 07 May 2020 20:48:20 -0400 The White House shelved a step-by-step guide prepared by U.S. health officials to help states safely reopen mass transit and businesses closed by the coronavirus pandemic, an administration official said on Thursday. This report produced by Chris Dignam. Full Article
dan How Dangerous Is Bariatric Surgery? By www.medicinenet.com Published On :: Wed, 18 Mar 2020 00:00:00 PDT Title: How Dangerous Is Bariatric Surgery?Category: Procedures and TestsCreated: 3/18/2020 12:00:00 AMLast Editorial Review: 3/18/2020 12:00:00 AM Full Article
dan Is Thyroid Hormone Dangerously Overprescribed in Older Patients? By www.medicinenet.com Published On :: Thu, 2 Apr 2020 00:00:00 PDT Title: Is Thyroid Hormone Dangerously Overprescribed in Older Patients?Category: Health NewsCreated: 4/1/2020 12:00:00 AMLast Editorial Review: 4/2/2020 12:00:00 AM Full Article
dan Hospital Computer Keyboards May Spread Danger By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Hospital Computer Keyboards May Spread DangerCategory: Health NewsCreated: 5/4/2006 1:58:00 AMLast Editorial Review: 5/4/2006 1:57:33 AM Full Article
dan Extreme Obesity Linked to Dangerous Behaviors in Teens By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Extreme Obesity Linked to Dangerous Behaviors in TeensCategory: Health NewsCreated: 4/26/2011 1:55:00 PMLast Editorial Review: 4/27/2011 12:00:00 AM Full Article
dan Defeating Dandruff By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Defeating DandruffCategory: Health NewsCreated: 4/28/2012 11:00:00 AMLast Editorial Review: 4/30/2012 12:00:00 AM Full Article
dan Blind Cords Pose Danger to Toddlers, Doctors Warn By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Blind Cords Pose Danger to Toddlers, Doctors WarnCategory: Health NewsCreated: 4/30/2013 10:35:00 AMLast Editorial Review: 4/30/2013 12:00:00 AM Full Article
dan HIV 'Cure' Looks 'Promising,' Danish Scientists Contend By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: HIV 'Cure' Looks 'Promising,' Danish Scientists ContendCategory: Health NewsCreated: 4/29/2013 12:35:00 PMLast Editorial Review: 4/30/2013 12:00:00 AM Full Article
dan Pot-Booze Combo More Dangerous for Teen Drivers Than Alcohol Alone By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Pot-Booze Combo More Dangerous for Teen Drivers Than Alcohol AloneCategory: Health NewsCreated: 4/28/2014 9:35:00 AMLast Editorial Review: 4/28/2014 12:00:00 AM Full Article
dan Health Tip: Batteries May Be Dangerous for Kids By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Health Tip: Batteries May Be Dangerous for KidsCategory: Health NewsCreated: 5/2/2014 7:35:00 AMLast Editorial Review: 5/2/2014 12:00:00 AM Full Article
dan Phone-Focused Parents a Danger to Their Kids at Playground By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Phone-Focused Parents a Danger to Their Kids at PlaygroundCategory: Health NewsCreated: 4/25/2015 12:00:00 AMLast Editorial Review: 4/27/2015 12:00:00 AM Full Article
dan Businesses Should Be Mindful of Zika Danger to Workers, CDC Says By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Businesses Should Be Mindful of Zika Danger to Workers, CDC SaysCategory: Health NewsCreated: 4/22/2016 12:00:00 AMLast Editorial Review: 4/25/2016 12:00:00 AM Full Article
dan Sleeping Pills Boost Danger of Falls, Fractures in Older Users By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Sleeping Pills Boost Danger of Falls, Fractures in Older UsersCategory: Health NewsCreated: 5/2/2017 12:00:00 AMLast Editorial Review: 5/3/2017 12:00:00 AM Full Article
dan FDA Warns of Tattoo Dangers By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: FDA Warns of Tattoo DangersCategory: Health NewsCreated: 5/5/2017 12:00:00 AMLast Editorial Review: 5/5/2017 12:00:00 AM Full Article
dan Red Wine Antioxidant Might Help Diabetics' Arteries By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Red Wine Antioxidant Might Help Diabetics' ArteriesCategory: Health NewsCreated: 5/4/2017 12:00:00 AMLast Editorial Review: 5/5/2017 12:00:00 AM Full Article
dan FDA Cracks Down on Dangerous E-Cig Liquids That Resemble Cookies, Candy By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: FDA Cracks Down on Dangerous E-Cig Liquids That Resemble Cookies, CandyCategory: Health NewsCreated: 5/1/2018 12:00:00 AMLast Editorial Review: 5/2/2018 12:00:00 AM Full Article
dan For People With Autism, Encounters With Police Can Turn Dangerous By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: For People With Autism, Encounters With Police Can Turn DangerousCategory: Health NewsCreated: 5/3/2019 12:00:00 AMLast Editorial Review: 5/3/2019 12:00:00 AM Full Article
dan Early High School Start Times May Hurt Attendance By www.medicinenet.com Published On :: Mon, 4 May 2020 00:00:00 PDT Title: Early High School Start Times May Hurt AttendanceCategory: Health NewsCreated: 5/1/2020 12:00:00 AMLast Editorial Review: 5/4/2020 12:00:00 AM Full Article
dan More Guidance on Inpatient Management of Blood Glucose in COVID-19 By www.webmd.com Published On :: Wed, 06 May 2020 12:05:04 EST Two new graphics from Diabetes UK's COVID-19 task force address inpatient use of subcutaneous insulin for managing hyperglycemia and ketoacidosis when intravenous equipment is unavailable. Full Article
dan The Danger of Internet Challenges By www.webmd.com Published On :: Fri, 08 May 2020 14:52:42 EST A child psychologist advises parents to address the threat of internet challenges with continual, preemptive conversations with kids -- and with special phone settings. Full Article
dan Updated guidance on data deposit and linking in PMC By www.ncbi.nlm.nih.gov Published On :: Mon, 30 Oct 2017 08:00:00 EST In response to the growing interest in the availability of data associated with articles, PMC is reviewing current practices around data and seeking feedback on how to best serve the data needs of the research community.As part of these efforts, the PMC policy statement on supplementary data was recently updated to more clearly articulate the requirement that any supplementary data (images, tables, video, or other documents / files) that are associated with an article must be deposited in PMC with an article. The search filter "has suppdata[filter]" can be used in PMC to discover records with associated supplementary data files.In addition to providing supplementary data with an article, NLM is also encouraging journals and authors to make research data available in a public repository and include the relevant data citation(s) in the paper. Guidance for PMC data providers on tagging data citations is available in the Tagging Guidelines. This guidance is based on the JATS4R recommendations on data citations.Starting this month, the NIH Manuscript Submission (NIHMS) system will also accept deposits of small datasets accompanying deposits of funded author manuscripts for inclusion of PMC. (Guidance for authors is available in the NIHMS FAQ.)If you have suggestions on future directions in data for PMC to consider, please let us know at pubmedcentral@ncbi.nlm.nih.gov. Full Article
dan PMC Tagging Guidance for Peer Review Documents Now Available By www.ncbi.nlm.nih.gov Published On :: Wed, 31 Jul 2019 08:00:00 EST Peer review documents, including review reports and editor decision letters, are increasingly being published along with the articles they review. This practice is intended to make the publishing process more transparent. To support these efforts, PMC’s Tagging Guidelines have been updated to include the tagging of peer review documents. NLM encourages PMC-participating publishers, journals, and data providers to review this guidance. Please contact us at pubmedcentral@ncbi.nlm.nih.gov if you have any questions. Full Article
dan Prescription-Strength Steroid Creams Sold Over-the-Counter Can Be Dangerous By www.medicinenet.com Published On :: Fri, 24 Jan 2020 00:00:00 PDT Title: Prescription-Strength Steroid Creams Sold Over-the-Counter Can Be DangerousCategory: Health NewsCreated: 1/23/2020 12:00:00 AMLast Editorial Review: 1/24/2020 12:00:00 AM Full Article
dan Blood Pressure Dips Upon Standing Might Not Be as Dangerous as Thought By www.medicinenet.com Published On :: Wed, 29 Jan 2020 00:00:00 PDT Title: Blood Pressure Dips Upon Standing Might Not Be as Dangerous as ThoughtCategory: Health NewsCreated: 1/28/2020 12:00:00 AMLast Editorial Review: 1/29/2020 12:00:00 AM Full Article
dan 'Couch Potato' Lifestyle Poses Danger to Women's Hearts By www.medicinenet.com Published On :: Wed, 19 Feb 2020 00:00:00 PDT Title: 'Couch Potato' Lifestyle Poses Danger to Women's HeartsCategory: Health NewsCreated: 2/18/2020 12:00:00 AMLast Editorial Review: 2/19/2020 12:00:00 AM Full Article
dan How Dangerous Is General Anesthesia? By www.medicinenet.com Published On :: Tue, 7 Apr 2020 00:00:00 PDT Title: How Dangerous Is General Anesthesia?Category: Procedures and TestsCreated: 3/5/2020 12:00:00 AMLast Editorial Review: 4/7/2020 12:00:00 AM Full Article
dan FDA Warns of Defective EpiPen Dangers By www.medicinenet.com Published On :: Thu, 26 Mar 2020 00:00:00 PDT Title: FDA Warns of Defective EpiPen DangersCategory: Health NewsCreated: 3/25/2020 12:00:00 AMLast Editorial Review: 3/26/2020 12:00:00 AM Full Article
dan Ask Grandma to Dance to Boost Her Mood And Strengthen Your Bonds By www.medicinenet.com Published On :: Mon, 20 Apr 2020 00:00:00 PDT Title: Ask Grandma to Dance to Boost Her Mood And Strengthen Your BondsCategory: Health NewsCreated: 4/17/2020 12:00:00 AMLast Editorial Review: 4/20/2020 12:00:00 AM Full Article
dan Dangerously Hot Days for U.S. Farm Workers Could Double by 2050 By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Dangerously Hot Days for U.S. Farm Workers Could Double by 2050Category: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
dan Phototropin2 Contributes to the Chloroplast Avoidance Response at the Chloroplast-Plasma Membrane Interface By www.plantphysiol.org Published On :: 2020-05-08T08:30:48-07:00 Blue-light-induced chloroplast movements play an important role in maximizing light utilization for photosynthesis in plants. Under a weak light condition, chloroplasts accumulate to the cell surface to capture light efficiently (chloroplast accumulation response). Conversely, chloroplasts escape from strong light and move to the side wall to reduce photodamage (chloroplast avoidance response). The blue light receptor phototropin (phot) regulates these chloroplast movements and optimizes leaf photosynthesis by controlling other responses in addition to chloroplast movements. Seed plants such as Arabidopsis (Arabidopsis thaliana) have phot1 and phot2. They redundantly mediate phototropism, stomatal opening, leaf flattening, and the chloroplast accumulation response. However, the chloroplast avoidance response is induced by strong blue light and regulated primarily by phot2. Phots are localized mainly on the plasma membrane. However, a substantial amount of phot2 resides on the chloroplast outer envelope. Therefore, differentially localized phot2 might have different functions. To determine the functions of plasma membrane- and chloroplast envelope-localized phot2, we tethered it to these structures with their respective targeting signals. Plasma membrane-localized phot2 regulated phototropism, leaf flattening, stomatal opening, and chloroplast movements. Chloroplast envelope-localized phot2 failed to mediate phototropism, leaf flattening, and the chloroplast accumulation response but partially regulated the chloroplast avoidance response and stomatal opening. Based on the present and previous findings, we propose that phot2 localized at the interface between the plasma membrane and the chloroplasts is required for the chloroplast avoidance response and possibly for stomatal opening as well. Full Article
dan EPSIN1 Contributes to Plant Immunity by Modulating the Abundance of Pattern Recognition Receptors at the Plasma Membrane By www.plantphysiol.org Published On :: 2020-05-08T08:30:48-07:00 Full Article
dan NF-{kappa}B and Keap1 Interaction Represses Nrf2-Mediated Antioxidant Response in Rabbit Hemorrhagic Disease Virus Infection [Pathogenesis and Immunity] By jvi.asm.org Published On :: 2020-05-04T08:00:46-07:00 The rabbit hemorrhagic disease virus (RHDV), which belongs to the family Caliciviridae and the genus Lagovirus, causes lethal fulminant hepatitis in rabbits. RHDV decreases the activity of antioxidant enzymes regulated by Nrf2 in the liver. Antioxidants are important for the maintenance of cellular integrity and cytoprotection. However, the mechanism underlying the regulation of the Nrf2-antioxidant response element (ARE) signaling pathway by RHDV remains unclear. Using isobaric tags for relative and absolute quantification (iTRAQ) technology, the current study demonstrated that RHDV inhibits the induction of ARE-regulated genes and increases the expression of the p50 subunit of the NF-B transcription factor. We showed that RHDV replication causes a remarkable increase in reactive oxygen species (ROS), which is simultaneously accompanied by a significant decrease in Nrf2. It was found that nuclear translocation of Keap1 plays a key role in the nuclear export of Nrf2, leading to the inhibition of Nrf2 transcriptional activity. The p50 protein partners with Keap1 to form the Keap1-p50/p65 complex, which is involved in the nuclear translocation of Keap1. Moreover, upregulation of Nrf2 protein levels in liver cell nuclei by tert-butylhydroquinone (tBHQ) delayed rabbit deaths due to RHDV infection. Considered together, our findings suggest that RHDV inhibits the Nrf2-dependent antioxidant response via nuclear translocation of Keap1-NF-B complex and nuclear export of Nrf2 and provide new insight into the importance of oxidative stress during RHDV infection. IMPORTANCE Recent studies have reported that rabbit hemorrhagic disease virus (RHDV) infection reduced Nrf2-related antioxidant function. However, the regulatory mechanisms underlying this process remain unclear. The current study showed that the NF-B p50 subunit partners with Keap1 to form the Keap1-NF-B complex, which plays a key role in the inhibition of Nrf2 transcriptional activity. More importantly, upregulated Nrf2 activity delayed the death of RHDV-infected rabbits, strongly indicating the importance of oxidative damage during RHDV infection. These findings may provide novel insights into the pathogenesis of RHDV. Full Article
dan Distribution of Ventilation Measured by Electrical Impedance Tomography in Critically Ill Children By rc.rcjournal.com Published On :: 2020-04-28T00:42:49-07:00 BACKGROUND:Electrical impedance tomography (EIT) is a noninvasive, portable lung imaging technique that provides functional distribution of ventilation. We aimed to describe the relationship between the distribution of ventilation by mode of ventilation and level of oxygenation impairment in children who are critically ill. We also aimed to describe the safety of EIT application.METHODS:A prospective observational study of EIT images obtained from subjects in the pediatric ICU. Images were categorized by whether the subjects were on intermittent mandatory ventilation (IMV), continuous spontaneous ventilation, or no positive-pressure ventilation. Images were categorized by the level of oxygenation impairment when using SpO2/FIO2. Distribution of ventilation is described by the center of ventilation.RESULTS:Sixty-four images were obtained from 25 subjects. Forty-two images obtained during IMV with a mean ± SD center of ventilation of 55 ± 6%, 14 images during continuous spontaneous ventilation with a mean ± SD center of ventilation of 48.1 ± 11%, and 8 images during no positive-pressure ventilation with a mean ± SD center of ventilation of 47.5 ± 10%. Seventeen images obtained from subjects with moderate oxygenation impairment with a mean ± SD center of ventilation of 59.3 ± 1.9%, 12 with mild oxygenation impairment with a mean ± SD center of ventilation of 52.6 ± 2.3%, and 4 without oxygenation impairment with a mean ± SD center of ventilation of 48.3 ± 4%. There was more ventral distribution of ventilation with IMV versus continuous spontaneous ventilation (P = .009), with IMV versus no positive-pressure ventilation (P = .01) cohorts, and with moderate oxygenation impairment versus cohorts without oxygenation impairment (P = .009). There were no adverse events related to the placement and use of EIT in our study.CONCLUSIONS:Children who had worse oxygen impairment or who received controlled modes of ventilation had more ventral distribution of ventilation than those without oxygen impairment or the subjects who were spontaneously breathing. The ability of EIT to detect changes in the distribution of ventilation in real time may allow for distribution-targeted mechanical ventilation strategies to be deployed proactively; however, future studies are needed to determine the effectiveness of such a strategy. Full Article
dan Tracking isotopically labeled oxidants using boronate-based redox probes [Methods and Resources] By www.jbc.org Published On :: 2020-05-08T03:41:14-07:00 Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products. Full Article
dan Evaluation of Cycle Threshold, Toxin Concentration, and Clinical Characteristics of Clostridioides difficile Infection in Patients with Discordant Diagnostic Test Results [Bacteriology] By jcm.asm.org Published On :: 2020-04-23T08:00:28-07:00 Clostridioides difficile infection (CDI) is one of the most common health care-associated infections that can cause significant morbidity and mortality. CDI diagnosis involves laboratory testing in conjunction with clinical assessment. The objective of this study was to assess the performance of various C. difficile tests and to compare clinical characteristics, Xpert C. difficile/Epi (PCR) cycle threshold (CT), and Singulex Clarity C. diff toxins A/B (Clarity) concentrations between groups with discordant test results. Unformed stool specimens from 200 hospitalized adults (100 PCR positive and 100 negative) were tested by cell cytotoxicity neutralization assay (CCNA), C. diff Quik Chek Complete (Quik Chek), Premier Toxins A and B, and Clarity. Clinical data, including CDI severity and CDI risk factors, were compared between discordant test results. Compared to CCNA, PCR had the highest sensitivity at 100% and Quik Chek had the highest specificity at 100%. Among clinical and laboratory data studied, prevalences of leukocytosis, prior antibiotic use, and hospitalizations were consistently higher across all subgroups in comparisons of toxin-positive to toxin-negative patients. Among PCR-positive samples, the median CT was lower in toxin-positive samples than in toxin-negative samples; however, CT ranges overlapped. Among Clarity-positive samples, the quantitative toxin concentration was significantly higher in toxin-positive samples than in toxin-negative samples as determined by CCNA and Quik Chek Toxin A and B. Laboratory tests for CDI vary in sensitivity and specificity. The quantitative toxin concentration may offer value in guiding CDI diagnosis and treatment. The presence of leukocytosis, prior antibiotic use, and previous hospitalizations may assist with CDI diagnosis, while other clinical parameters may not be consistently reliable. Full Article
dan Rapid evolution of piRNA-mediated silencing of an invading transposable element was driven by abundant de novo mutations [RESEARCH] By genome.cshlp.org Published On :: 2020-04-27T12:09:24-07:00 The regulation of transposable element (TE) activity by small RNAs is a ubiquitous feature of germlines. However, despite the obvious benefits to the host in terms of ensuring the production of viable gametes and maintaining the integrity of the genomes they carry, it remains controversial whether TE regulation evolves adaptively. We examined the emergence and evolutionary dynamics of repressor alleles after P-elements invaded the Drosophila melanogaster genome in the mid-twentieth century. In many animals including Drosophila, repressor alleles are produced by transpositional insertions into piRNA clusters, genomic regions encoding the Piwi-interacting RNAs (piRNAs) that regulate TEs. We discovered that ~94% of recently collected isofemale lines in the Drosophila melanogaster Genetic Reference Panel (DGRP) contain at least one P-element insertion in a piRNA cluster, indicating that repressor alleles are produced by de novo insertion at an exceptional rate. Furthermore, in our sample of approximately 200 genomes, we uncovered no fewer than 80 unique P-element insertion alleles in at least 15 different piRNA clusters. Finally, we observe no footprint of positive selection on P-element insertions in piRNA clusters, suggesting that the rapid evolution of piRNA-mediated repression in D. melanogaster was driven primarily by mutation. Our results reveal for the first time how the unique genetic architecture of piRNA production, in which numerous piRNA clusters can encode regulatory small RNAs upon transpositional insertion, facilitates the nonadaptive rapid evolution of repression. Full Article
dan Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control [RESEARCH] By genome.cshlp.org Published On :: 2020-04-27T12:09:23-07:00 Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A, and RAD21, cohesin in somatic cells contains one of two orthologous STAG subunits, STAG1 or STAG2. How these variable subunits affect the function of the cohesin complex is still unclear. STAG1- and STAG2-cohesin were initially proposed to organize cohesion at telomeres and centromeres, respectively. Here, we uncover redundant and specific roles of STAG1 and STAG2 in gene regulation and chromatin looping using HCT116 cells with an auxin-inducible degron (AID) tag fused to either STAG1 or STAG2. Following rapid depletion of either subunit, we perform high-resolution Hi-C, gene expression, and sequential ChIP studies to show that STAG1 and STAG2 do not co-occupy individual binding sites and have distinct ways by which they affect looping and gene expression. These findings are further supported by single-molecule localizations via direct stochastic optical reconstruction microscopy (dSTORM) super-resolution imaging. Since somatic and congenital mutations of the STAG subunits are associated with cancer (STAG2) and intellectual disability syndromes with congenital abnormalities (STAG1 and STAG2), we verified STAG1-/STAG2-dependencies using human neural stem cells, hence highlighting their importance in particular disease contexts. Full Article
dan Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life By openres.ersjournals.com Published On :: 2020-04-19T07:30:11-07:00 Electronic cigarettes (e-cigarettes) have been used in many countries for >10 years and in this time, there has been a division of opinions amongst both the general public and health professionals regarding the benefit or harms of e-cigarettes. Prior to the reporting of a new phenomenon known as vaping-associated pulmonary injury (VAPI), public opinion about the relative harm of e-cigarettes were increasing but they were perceived as less harmful than cigarettes by one third of people [1]. The recent cases of severe illness and death attributable to VAPI were first described in September 2019 [2]. VAPI appears to be related to either the addition of cannabis/cannabis derivates or vitamin E acetate [3], and as such has not caused radical swing away from the use of e-cigarettes without cannabis or cannabis derivates. Full Article
dan Guidance for psychological therapists: information for GPs advising patients on antidepressant withdrawal By bjgp.org Published On :: 2020-04-30T16:04:41-07:00 Full Article
dan Efficacy and Safety of Use of the Fasting Algorithm for Singaporeans With Type 2 Diabetes (FAST) During Ramadan: A Prospective, Multicenter, Randomized Controlled Trial [Original Research] By www.annfammed.org Published On :: 2020-03-09T14:00:11-07:00 PURPOSE We aimed to evaluate the efficacy and safety of use of the Fasting Algorithm for Singaporeans with Type 2 Diabetes (FAST) during Ramadan. METHODS We performed a prospective, multicenter, randomized controlled trial. The inclusion criteria were age ≥21 years, baseline glycated hemoglobin (HbA1c) level ≤9.5%, and intention to fast for ≥10 days during Ramadan. Exclusion criteria included baseline estimated glomerular filtration rate <30 mL/min, diabetes-related hospitalization, and short-term corticosteroid therapy. Participants were randomized to intervention (use of FAST) or control (usual care without FAST) groups. Efficacy outcomes were HbA1c level and fasting blood glucose and postprandial glucose changes, and the safety outcome was incidence of major or minor hypoglycemia during the Ramadan period. Glycemic variability and diabetes distress were also investigated. Linear mixed models were constructed to assess changes. RESULTS A total of 97 participants were randomized (intervention: n = 46, control: n = 51). The HbA1c improvement during Ramadan was 4 times greater in the intervention group (–0.4%) than in the control group (–0.1%) (P = .049). The mean fasting blood glucose level decreased in the intervention group (–3.6 mg/dL) and increased in the control group (+20.9 mg/dL) (P = .034). The mean postprandial glucose level showed greater improvement in the intervention group (–16.4 mg/dL) compared to the control group (–2.3 mg/dL). There were more minor hypoglycemic events based on self-monitered blood glucose readings in the control group (intervention: 4, control: 6; P = .744). Glycemic variability was not significantly different between the 2 groups (P = .284). No between-group differences in diabetes distress were observed (P = .479). CONCLUSIONS Our findings emphasize the importance of efficacious, safe, and culturally tailored epistemic tools for diabetes management. Full Article
dan Bioimpedance Guided Fluid Management in Peritoneal Dialysis: A Randomized Controlled Trial By cjasn.asnjournals.org Published On :: 2020-05-07T10:00:25-07:00 Background and objectives Bioelectrical impedance analysis (BIA) devices can help assess volume overload in patients receiving maintenance peritoneal dialysis. However, the effects of BIA on the short-term hard end points of peritoneal dialysis lack consistency. This study aimed to test whether BIA-guided fluid management could improve short-term outcomes in patients on peritoneal dialysis. Design, setting, participants, & measurements A single-center, open-labeled, randomized, controlled trial was conducted. Patients on prevalent peritoneal dialysis with volume overload were recruited from July 1, 2013 to March 30, 2014 and followed for 1 year in the initial protocol. All participants with volume overload were 1:1 randomized to the BIA-guided arm (BIA and traditional clinical methods) and control arm (only traditional clinical methods). The primary end point was all-cause mortality and secondary end points were cardiovascular disease mortality and technique survival. Results A total of 240 patients (mean age, 49 years; men, 51%; diabetic, 21%, 120 per group) were enrolled. After 1-year follow-up, 11(5%) patients died (three in BIA versus eight in control) and 21 patients were permanently transferred to hemodialysis (eight in BIA versus 13 in control). The rate of extracellular water/total body water decline in the BIA group was significantly higher than that in the control group. The 1-year patient survival rates were 96% and 92% in BIA and control groups, respectively. No significant statistical differences were found between patients randomized to the BIA-guided or control arm in terms of patient survival, cardiovascular disease mortality, and technique survival (P>0.05). Conclusions Although BIA-guided fluid management improved the fluid overload status better than the traditional clinical method, no significant effect was found on 1-year patient survival and technique survival in patients on peritoneal dialysis. Full Article
dan A Pharmacologic "Stress Test" for Assessing Select Antioxidant Defenses in Patients with CKD By cjasn.asnjournals.org Published On :: 2020-05-07T10:00:25-07:00 Background and objectives Oxidative stress is a hallmark and mediator of CKD. Diminished antioxidant defenses are thought to be partly responsible. However, there is currently no way to prospectively assess antioxidant defenses in humans. Tin protoporphyrin (SnPP) induces mild, transient oxidant stress in mice, triggering increased expression of select antioxidant proteins (e.g., heme oxygenase 1 [HO-1], NAD[P]H dehydrogenase [quinone] 1 [NQO1], ferritin, p21). Hence, we tested the hypothesis that SnPP can also variably increase these proteins in humans and can thus serve as a pharmacologic "stress test" for gauging gene responsiveness and antioxidant reserves. Design, setting, participants, & measurements A total of 18 healthy volunteers and 24 participants with stage 3 CKD (n=12; eGFR 30–59 ml/min per 1.73 m2) or stage 4 CKD (n=12; eGFR 15–29 ml/min per 1.73 m2) were injected once with SnPP (9, 27, or 90 mg). Plasma and/or urinary antioxidant proteins were measured at baseline and for up to 4 days post-SnPP dosing. Kidney safety was gauged by serial measurements of BUN, creatinine, eGFR, albuminuria, and four urinary AKI biomarkers (kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, cystatin C, and N-acetyl glucosaminidase). Results Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (r=–0.85 to –0.95). All four proteins manifested statistically significant dose- and time-dependent elevations after SnPP injection. However, marked intersubject differences were observed. p21 responses to high-dose SnPP and HO-1 responses to low-dose SnPP were significantly suppressed in participants with CKD versus healthy volunteers. SnPP was well tolerated by all participants, and no evidence of nephrotoxicity was observed. Conclusions SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease. Clinical Trial registry name and registration number A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3–4 Chronic Kidney Disease, NCT0363002 and NCT03893799 Full Article
dan The Elusive Promise of Bioimpedance in Fluid Management of Patients Undergoing Dialysis By cjasn.asnjournals.org Published On :: 2020-05-07T10:00:25-07:00 Full Article
dan Unexpected Abundance and Diversity of Phototrophs in Mats from Morphologically Variable Microbialites in Great Salt Lake, Utah [Microbial Ecology] By aem.asm.org Published On :: 2020-05-05T08:00:35-07:00 Microbial mat communities are associated with extensive (~700 km2) and morphologically variable carbonate structures, termed microbialites, in the hypersaline Great Salt Lake (GSL), Utah. However, whether the composition of GSL mat communities covaries with microbialite morphology and lake environment is unknown. Moreover, the potential adaptations that allow the establishment of these extensive mat communities at high salinity (14% to 17% total salts) are poorly understood. To address these questions, microbial mats were sampled from seven locations in the south arm of GSL representing different lake environments and microbialite morphologies. Despite the morphological differences, microbialite-associated mats were taxonomically similar and were dominated by the cyanobacterium Euhalothece and several heterotrophic bacteria. Metagenomic sequencing of a representative mat revealed Euhalothece and subdominant Thiohalocapsa populations that harbor the Calvin cycle and nitrogenase, suggesting they supply fixed carbon and nitrogen to heterotrophic bacteria. Fifteen of the next sixteen most abundant taxa are inferred to be aerobic heterotrophs and, surprisingly, harbor reaction center, rhodopsin, and/or bacteriochlorophyll biosynthesis proteins, suggesting aerobic photoheterotrophic (APH) capabilities. Importantly, proteins involved in APH are enriched in the GSL community relative to that in microbialite mat communities from lower salinity environments. These findings indicate that the ability to integrate light into energy metabolism is a key adaptation allowing for robust mat development in the hypersaline GSL. IMPORTANCE The earliest evidence of life on Earth is from organosedimentary structures, termed microbialites, preserved in 3.481-billion-year-old (Ga) rocks. Phototrophic microbial mats form in association with an ~700-km2 expanse of morphologically diverse microbialites in the hypersaline Great Salt Lake (GSL), Utah. Here, we show taxonomically similar microbial mat communities are associated with morphologically diverse microbialites across the lake. Metagenomic sequencing reveals an abundance and diversity of autotrophic and heterotrophic taxa capable of harvesting light energy to drive metabolism. The unexpected abundance of and diversity in the mechanisms of harvesting light energy observed in GSL mat populations likely function to minimize niche overlap among coinhabiting taxa, provide a mechanism(s) to increase energy yield and osmotic balance during salt stress, and enhance fitness. Together, these physiological benefits promote the formation of robust mats that, in turn, influence the formation of morphologically diverse microbialite structures that can be imprinted in the rock record. Full Article
dan Temperature and Nutrient Levels Correspond with Lineage-Specific Microdiversification in the Ubiquitous and Abundant Freshwater Genus Limnohabitans [Environmental Microbiology] By aem.asm.org Published On :: 2020-05-05T08:00:35-07:00 Most freshwater bacterial communities are characterized by a few dominant taxa that are often ubiquitous across freshwater biomes worldwide. Our understanding of the genomic diversity within these taxonomic groups is limited to a subset of taxa. Here, we investigated the genomic diversity that enables Limnohabitans, a freshwater genus key in funneling carbon from primary producers to higher trophic levels, to achieve abundance and ubiquity. We reconstructed eight putative Limnohabitans metagenome-assembled genomes (MAGs) from stations located along broad environmental gradients existing in Lake Michigan, part of Earth’s largest surface freshwater system. De novo strain inference analysis resolved a total of 23 strains from these MAGs, which strongly partitioned into two habitat-specific clusters with cooccurring strains from different lineages. The largest number of strains belonged to the abundant LimB lineage, for which robust in situ strain delineation had not previously been achieved. Our data show that temperature and nutrient levels may be important environmental parameters associated with microdiversification within the Limnohabitans genus. In addition, strains predominant in low- and high-phosphorus conditions had larger genomic divergence than strains abundant under different temperatures. Comparative genomics and gene expression analysis yielded evidence for the ability of LimB populations to exhibit cellular motility and chemotaxis, a phenotype not yet associated with available Limnohabitans isolates. Our findings broaden historical marker gene-based surveys of Limnohabitans microdiversification and provide in situ evidence of genome diversity and its functional implications across freshwater gradients. IMPORTANCE Limnohabitans is an important bacterial taxonomic group for cycling carbon in freshwater ecosystems worldwide. Here, we examined the genomic diversity of different Limnohabitans lineages. We focused on the LimB lineage of this genus, which is globally distributed and often abundant, and its abundance has shown to be largely invariant to environmental change. Our data show that the LimB lineage is actually comprised of multiple cooccurring populations for which the composition and genomic characteristics are associated with variations in temperature and nutrient levels. The gene expression profiles of this lineage suggest the importance of chemotaxis and motility, traits that had not yet been associated with the Limnohabitans genus, in adapting to environmental conditions. Full Article