led 'Justice finally prevailed' in Michael Flynn case: WH By feeds.reuters.com Published On :: Fri, 08 May 2020 15:02:19 -0400 White House spokeswoman Kayleigh McEnany on Friday said it appears that the FBI 'manufactured' a crime in the case of President Trump's former national security adviser Michael Flynn, after the Department of Justice moved to drop the case on Thursday. Full Article
led Mummified skin suggests duck-billed dinosaurs were grey like elephants By www.newscientist.com Published On :: Sat, 11 Jan 2020 08:00:04 +0000 The mummified remains of a duck-billed dinosaur contain a grey pigment, suggesting it was grey, although other pigments may have been lost during fossilisation Full Article
led The smuggled Mongolian dinosaur fossil that seemed too good to be true By www.newscientist.com Published On :: Wed, 12 Feb 2020 18:00:00 +0000 When a bizarre fossil appeared for sale in Europe, it looked so odd it had to be fake. But a high-tech investigation introduced us to Halzkaraptor escullei – part velociraptor, part penguin Full Article
led Seagulls are more likely to pick up food that humans have handled By www.newscientist.com Published On :: Wed, 26 Feb 2020 00:01:21 +0000 Seagulls are known for aggressively attempting to swipe people's food, and it seems that when given the choice between identical meals, they favour the one handled by humans Full Article
led Earth's first life may have fuelled itself with a metal metabolism By www.newscientist.com Published On :: Thu, 16 Apr 2020 10:00:03 +0000 The first living organisms had to make essential carbon-based chemicals, and they may have done it by harnessing the chemical power of metals like nickel Full Article
led Massive Spinosaurus dinosaur swam through water propelled by its tail By www.newscientist.com Published On :: Wed, 29 Apr 2020 16:00:45 +0000 A well-preserved fossilised tail from Spinosaurus suggests this massive dinosaur may have been able to propel itself and hunt for prey in the water Full Article
led Investors fled bonds as well as stocks in March By feeds.reuters.com Published On :: Wed, 15 Apr 2020 16:52:20 -0400 Investors withdrew record amounts of money from bond and equity funds in March while money market funds showed record inflows, as the prospect of a massive economic downturn due to coronavirus... Full Article PersonalFinance
led 'Justice finally prevailed' in Michael Flynn case: WH By www.reuters.com Published On :: Fri, 08 May 2020 15:02:19 -0400 White House spokeswoman Kayleigh McEnany on Friday said it appears that the FBI 'manufactured' a crime in the case of President Trump's former national security adviser Michael Flynn, after the Department of Justice moved to drop the case on Thursday. Full Article
led The hidden cities revealed by lasers By www.newscientist.com Published On :: Fri, 01 Feb 2019 10:59:54 +0000 Through the jungle, airborne lasers have spotted ruins of long-lost ancient civilisations in Asia. Archaeologist Damian Evans reveals all. Full Article
led Today's global warming is unparalleled in the past 2000 years By www.newscientist.com Published On :: Wed, 24 Jul 2019 18:00:01 +0000 We now know that past periods when Earth cooled and warmed were only regional. The finding rebuffs the myth that today's planet-wide warming is a natural blip Full Article
led Ancient Egyptians saw the sky as crumbling iron tub filled with water By www.newscientist.com Published On :: Mon, 04 May 2020 10:00:35 +0000 A fresh look at the world’s oldest religious texts suggests ancient Egyptians saw the sky as a water-filled iron container from which chunks fell to Earth as meteorites Full Article
led The smuggled Mongolian dinosaur fossil that seemed too good to be true By www.newscientist.com Published On :: Wed, 12 Feb 2020 18:00:00 +0000 When a bizarre fossil appeared for sale in Europe, it looked so odd it had to be fake. But a high-tech investigation introduced us to Halzkaraptor escullei – part velociraptor, part penguin Full Article
led EU Commission calls for state guarantees for vouchers for cancelled travel By feeds.reuters.com Published On :: Sat, 09 May 2020 05:00:04 -0400 The European Commission will tell countries in the European Union to provide state guarantees for travel vouchers during the coronavirus pandemic, if they prefer people to accept the vouchers instead of cash refunds, according to a strategy document seen by Reuters. Full Article companyNews
led 'Justice finally prevailed' in Michael Flynn case: WH By feeds.reuters.com Published On :: Fri, 08 May 2020 15:02:19 -0400 White House spokeswoman Kayleigh McEnany on Friday said it appears that the FBI 'manufactured' a crime in the case of President Trump's former national security adviser Michael Flynn, after the Department of Justice moved to drop the case on Thursday. Full Article
led BCG vaccine being trialled as potential protection against covid-19 By www.newscientist.com Published On :: Thu, 23 Apr 2020 13:00:54 +0000 A long-standing hypothesis suggests the BCG vaccine also serves to generally enhance the immune system, meaning it could protect against covid-19, and trials are under way to find out Full Article
led Names of UK's coronavirus science advisers to be revealed By www.newscientist.com Published On :: Mon, 27 Apr 2020 17:02:26 +0000 The membership of the UK's Scientific Advisory Group for Emergencies has so far been kept secret, but a list of names will soon be published, the UK's chief scientific adviser has said Full Article
led Massive Spinosaurus dinosaur swam through water propelled by its tail By www.newscientist.com Published On :: Wed, 29 Apr 2020 16:00:45 +0000 A well-preserved fossilised tail from Spinosaurus suggests this massive dinosaur may have been able to propel itself and hunt for prey in the water Full Article
led Ancient Egyptians saw the sky as crumbling iron tub filled with water By www.newscientist.com Published On :: Mon, 04 May 2020 10:00:35 +0000 A fresh look at the world’s oldest religious texts suggests ancient Egyptians saw the sky as a water-filled iron container from which chunks fell to Earth as meteorites Full Article
led How the covid-19 pandemic has led to a flood of misleading science By www.newscientist.com Published On :: Wed, 06 May 2020 14:25:00 +0000 Amid the global coronavirus outbreak, a second epidemic of preliminary, unverified and misinterpreted research has broken out. Can it be fixed? Full Article
led 'Justice finally prevailed' in Michael Flynn case: WH By www.reuters.com Published On :: Fri, 08 May 2020 15:02:19 -0400 White House spokeswoman Kayleigh McEnany on Friday said it appears that the FBI 'manufactured' a crime in the case of President Trump's former national security adviser Michael Flynn, after the Department of Justice moved to drop the case on Thursday. Full Article
led Health Tip: Prevent a Pulled Hamstring By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Health Tip: Prevent a Pulled HamstringCategory: Health NewsCreated: 4/28/2007 2:00:00 AMLast Editorial Review: 4/30/2007 12:00:00 AM Full Article
led After Teeth Are Pulled, Platelet-Rich Plasma May Speed Healing By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: After Teeth Are Pulled, Platelet-Rich Plasma May Speed HealingCategory: Health NewsCreated: 4/23/2010 12:10:00 PMLast Editorial Review: 4/26/2010 12:00:00 AM Full Article
led Recalled Cucumbers in Your Fridge? By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Recalled Cucumbers in Your Fridge?Category: Health NewsCreated: 4/26/2011 1:54:00 PMLast Editorial Review: 4/27/2011 12:00:00 AM Full Article
led Knowledge Is Power for Patients With Heart Failure By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Knowledge Is Power for Patients With Heart FailureCategory: Health NewsCreated: 4/29/2015 12:00:00 AMLast Editorial Review: 4/30/2015 12:00:00 AM Full Article
led Chicken Patties Sold at Costco Recalled By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Chicken Patties Sold at Costco RecalledCategory: Health NewsCreated: 4/29/2017 12:00:00 AMLast Editorial Review: 5/1/2017 12:00:00 AM Full Article
led Dog Food Recalled After Tests Find Euthanasia Drug By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Dog Food Recalled After Tests Find Euthanasia DrugCategory: Health NewsCreated: 4/29/2017 12:00:00 AMLast Editorial Review: 5/1/2017 12:00:00 AM Full Article
led U.S. Workplaces Roiled by Post-Election Discord, Poll Finds By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: U.S. Workplaces Roiled by Post-Election Discord, Poll FindsCategory: Health NewsCreated: 5/3/2017 12:00:00 AMLast Editorial Review: 5/4/2017 12:00:00 AM Full Article
led Nearly 700,000 Infant Rocking Sleepers Recalled Due to Infant Deaths By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Nearly 700,000 Infant Rocking Sleepers Recalled Due to Infant DeathsCategory: Health NewsCreated: 4/29/2019 12:00:00 AMLast Editorial Review: 4/29/2019 12:00:00 AM Full Article
led EuroPCR 2020 Canceled as SCAI, SCCT, TVT Go Virtual By www.webmd.com Published On :: Wed, 06 May 2020 13:07:16 EST In a sign of the times and things to come, in-person cardiovascular society meetings pivot to virtual events. Full Article
led AHA News: Nearly Killed in OKC Bombing, She Vowed to Change Her Life By www.medicinenet.com Published On :: Fri, 17 Apr 2020 00:00:00 PDT Title: AHA News: Nearly Killed in OKC Bombing, She Vowed to Change Her LifeCategory: Health NewsCreated: 4/16/2020 12:00:00 AMLast Editorial Review: 4/17/2020 12:00:00 AM Full Article
led Pot Use Among U.S. Seniors Nearly Doubled in 3 Years By www.medicinenet.com Published On :: Tue, 25 Feb 2020 00:00:00 PDT Title: Pot Use Among U.S. Seniors Nearly Doubled in 3 YearsCategory: Health NewsCreated: 2/24/2020 12:00:00 AMLast Editorial Review: 2/25/2020 12:00:00 AM Full Article
led What Is a Choledochojejunostomy? By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: What Is a Choledochojejunostomy?Category: Procedures and TestsCreated: 5/6/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
led There's a Virus Spreading in U.S. That's Killed 10,000: The Flu By www.medicinenet.com Published On :: Fri, 7 Feb 2020 00:00:00 PDT Title: There's a Virus Spreading in U.S. That's Killed 10,000: The FluCategory: Health NewsCreated: 2/7/2020 12:00:00 AMLast Editorial Review: 2/7/2020 12:00:00 AM Full Article
led Knowledge, Attitudes and Practices of Dental Hygienists Regarding Diabetes Risk Assessments and Screenings By jdh.adha.org Published On :: 2020-04-30T12:39:03-07:00 Purpose: Untreated and poorly controlled diabetes causes increased levels of blood glucose associated with poor periodontal disease outcomes. Dental hygienists can play a significant role in screening patients for diabetes mellitus, leading to referral and early diagnosis. The purpose of this study was to determine the knowledge, attitudes, practices, and barriers faced by clinical dental hygienists regarding diabetes risk assessment and screenings.Methods: A mixed method design was used with a convenience sample of dental hygienists in clinical practice (n=316). A 32 item, electronic survey was validated at item-level, and participants were recruited through multiple dental hygiene Facebook groups. Descriptive statistics were used to analyze the data. The survey also included two open-ended attitude questions that were interpreted using thematic analysis to pinpoint common patterns within the data.Results: Dental hygienists had high knowledge scores regarding diabetes and oral health, although many were unaware of their states' specific statutes and regulations for screening practices. Nearly all (95.9%), were likely to educate and refer patients (82%), although fewer than half (40.9%), were likely to perform chairside screening for diabetes. Emergent themes for barriers to screening were time, money, patient acceptance/willingness, lack of education, not having the proper tools, and states' rules and regulations.Conclusion: Despite high knowledge scores regarding diabetes and oral health, there is a gap in regards to dental hygienists' willingness to perform diabetes screenings in a clinical setting. Dental hygienists should be capable of integrating chairside diabetes screening practices into the process of care with proper training. Full Article
led Acknowledgment of Invited Editors By mbio.asm.org Published On :: 2020-03-24T01:31:01-07:00 Full Article
led Acknowledgment of Reviewers By mbio.asm.org Published On :: 2020-03-24T01:31:01-07:00 Full Article
led Minnesota association acknowledges states ancestral lands, residents By thenationshealth.aphapublications.org Published On :: 2020-05-01T05:00:17-07:00 In a nod to the people who came before them — and those who still live among them — the Minnesota Public Health Association is acknowledging ancestral lands. Full Article
led Coupled hydraulic and mechanical model of surface uplift due to mine water rebound: implications for mine water heating and cooling schemes By sjg.lyellcollection.org Published On :: 2019-11-29T02:21:48-08:00 In order to establish sustainable heat loading (heat removal and storage) in abandoned flooded mine workings it is important to understand the geomechanical impact of the cyclical heat loading caused by fluid injection and extraction. This is particularly important where significantly more thermal loading is planned than naturally occurs. A simple calculation shows that the sustainable geothermal heat flux from abandoned coal mines can provide less than a tenth of Scotland's annual domestic heating demand. Any heat removal greater than the natural heat flux will lead to heat mining unless heat storage options are also considered. As a first step, a steady-state, fully saturated, 2D coupled hydromechanical model of a generalized section of pillar-and-stall workings has been created. Mine water rebound was modelled by increasing the hydrostatic pressure sequentially, in line with monitored mine water-level data from Midlothian, Scotland. The modelled uplift to water-level rise ratio of 1.4 mm m–1 is of the same order of magnitude (1 mm m–1) as that observed through interferometric synthetic aperture radar (InSAR) data in the coalfield due to mine water rebound. The modelled magnitude of shear stress at the pillar corners, as a result of horizontal and vertical displacement, is shown to increase linearly with water level. Mine heat systems are expected to cause smaller changes in pressure than those modelled but the results provide initial implications on the potential geomechanical impacts of mine water heat schemes which abstract or inject water and heat into pillar-and-stall coal mine workings. Thematic collection: This article is part of the SJG Collection on Early-Career Research available at: https://www.lyellcollection.org/cc/SJG-early-career-research Full Article
led Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective By erj.ersjournals.com Published On :: 2020-05-07T01:15:55-07:00 The current coronavirus 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, raises important questions as to whether pre-morbid use or continued administration of inhaled corticosteroids (ICS) affects the outcomes of acute respiratory infections due to coronavirus. Many physicians are concerned about whether individuals positive for SARS-CoV-2 and taking ICS should continue them or stop them, given that ICS are often regarded as immunosuppressive. A number of key questions arise. Are people with asthma or COPD at increased risk of developing COVID-19? Do ICS modify this risk, either increasing or decreasing it? Do ICS influence the clinical course of COVID-19? (figure 1). Whether ICS modify the risk of developing COVID-19 or the clinical course of COVID-19 in people who do not have lung disease should also be considered (figure 1). Full Article
led Looking back to go forward: adherence to inhaled therapy before biologic therapy in severe asthma By erj.ersjournals.com Published On :: 2020-05-07T01:15:55-07:00 For decades inhaled corticosteroids have been central to the management of asthma and are proven to be effective in maintaining symptom control, reducing exacerbations and preserving quality of life through mediation of airway inflammation. However, a small minority of patients have disease which is refractory to high dose inhaled corticosteroid (ICS) therapy and require additional oral corticosteroids to achieve acceptable control of symptoms and exacerbations. Severe asthma represents less than 10% of the total asthma population [1] but is the most serious, life-affecting and costly form of the condition [2]. Full Article
led Development of the Proximal-Anterior Skeletal Elements in the Mouse Hindlimb Is Regulated by a Transcriptional and Signaling Network Controlled by Sall4 [Developmental and Behavioral Genetics] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 The vertebrate limb serves as an experimental paradigm to study mechanisms that regulate development of the stereotypical skeletal elements. In this study, we simultaneously inactivated Sall4 using Hoxb6Cre and Plzf in mouse embryos, and found that their combined function regulates development of the proximal-anterior skeletal elements in hindlimbs. The Sall4; Plzf double knockout exhibits severe defects in the femur, tibia, and anterior digits, distinct defects compared to other allelic series of Sall4; Plzf. We found that Sall4 regulates Plzf expression prior to hindlimb outgrowth. Further expression analysis indicated that Hox10 genes and GLI3 are severely downregulated in the Sall4; Plzf double knockout hindlimb bud. In contrast, PLZF expression is reduced but detectable in Sall4; Gli3 double knockout limb buds, and SALL4 is expressed in the Plzf; Gli3 double knockout limb buds. These results indicate that Plzf, Gli3, and Hox10 genes downstream of Sall4, regulate femur and tibia development. In the autopod, we show that Sall4 negatively regulates Hedgehog signaling, which allows for development of the most anterior digit. Collectively, our study illustrates genetic systems that regulate development of the proximal-anterior skeletal elements in hindlimbs. Full Article
led Covert sleep-related biological processes are revealed by probabilistic analysis in Drosophila [Neuroscience] By www.pnas.org Published On :: 2020-05-05T10:31:24-07:00 Sleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters in Drosophila melanogaster have low temporal resolution and/or require disrupting sleep. Here we report analysis tools for high-resolution, noninvasive measurement of sleep pressure and depth from movement data. Probability of initiating activity,... Full Article
led Inhaled Corticosteroid Treatment in Chronic Obstructive Pulmonary Disease (COPD): Boon or Bane? By www.jabfm.org Published On :: 2020-03-16T09:31:37-07:00 Inhaled corticosteroid (ICS)–based therapy is often used for patients with chronic obstructive pulmonary disease (COPD). However, this approach is under scrutiny because of ICS overuse in patients for whom it is not recommended and because of concerns about adverse events, particularly pneumonia, with long-term ICS use. Evidence suggests ICS may be beneficial in specific patients, namely, those with high blood eosinophil counts (eg, ≥300 cells/µL) or who are at a high risk of exacerbations. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 ABCD assessment tool, these patients belong in group D. For these patients, recommended initial treatment includes ICS in combination with long-acting β2-agonists (LABAs) when blood eosinophil counts are ≥300 cells/µL or LABA + long-acting muscarinic antagonist (LAMA) when patients are highly symptomatic, that is, with greater dyspnea and/or exercise limitation. Follow-up treatments for patients with persistent dyspnea and/or exacerbations may include LABA + ICS, LABA + LAMA, or LABA + LAMA + ICS, with use of ICS being guided by blood eosinophil counts. In this review, differences in the inflammatory mechanism underlying COPD and asthma and the role of ICS treatment in COPD are summarized. Furthermore, findings from recent clinical trials where use of ICS-based dual or triple therapy in COPD was compared with LABA + LAMA therapy and trials in which ICS withdrawal was evaluated in patients with COPD are reviewed. Finally, a step-by-step guide for ICS withdrawal in patients who are unlikely to benefit from this treatment is proposed. A video of the author discussing the overall takeaway of the review article could be downloaded from the link provided: https://www.youtube.com/watch?v=Uq7Sr5jqPDI. Full Article
led Secondary osteon structural heterogeneity between the cranial and caudal cortices of the proximal humerus in white-tailed deer [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-05-04T02:24:22-07:00 Jack Nguyen and Meir M. BarakCortical bone remodeling is an ongoing process triggered by microdamage, where osteoclasts resorb existing bone and osteoblasts deposit new bone in the form of secondary osteons (Haversian systems). Previous studies revealed regional variance in Haversian systems structure and possibly material, between opposite cortices of the same bone. As bone mechanical properties depend on tissue structure and material, it is predicted that bone mechanical properties will vary in accordance with structural and material regional heterogeneity. To test this hypothesis, we analyzed the structure, mineral content and compressive stiffness of secondary bone from the cranial and caudal cortices of the white-tailed deer proximal humerus. We found significantly larger Haversian systems and canals in the cranial cortex but no significant difference in mineral content between the two cortices. Accordingly, we found no difference in compressive stiffness between the two cortices and thus our working hypothesis was rejected. Seeing that the deer humerus is curved and thus likely subjected to bending during habitual locomotion, we expect that similar to other curved long bones, the cranial cortex of the deer humerus is likely subjected primarily to tensile strains and the caudal cortex is likely subject primarily to compressive strains. Consequently, our results suggest that strain magnitude (larger in compression) and sign (compression vs. tension) affect differently the osteoclasts and osteoblasts in the BMU. Our results further suggest that osteoclasts are inhibited in regions of high compressive strains (creating smaller Haversian systems) while osteoblasts’ osteoid deposition and mineralization is not affected by strain magnitude and sign. Full Article
led Probiotics for the Prevention of Ventilator-Associated Pneumonia: A Meta-Analysis of Randomized Controlled Trials By rc.rcjournal.com Published On :: 2020-04-28T00:42:49-07:00 BACKGROUND:Ventilator-associated pneumonia (VAP) is a common and serious complication of mechanical ventilation. We conducted a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of probiotics for VAP prevention in patients who received mechanical ventilation.METHODS:We searched a number of medical literature databases to identify randomized controlled trials that compared probiotics with controls for VAP prevention. The results were expressed as odds ratios (OR) or mean differences with accompanying 95% CIs. Study-level data were pooled by using a random-effects model. Data syntheses were accomplished by using statistical software.RESULTS:Fourteen studies that involved 1,975 subjects met our inclusion criteria. Probiotic administration was associated with a reduction in VAP incidence among all 13 studies included in the meta-analysis (OR 0.62, 95% CI 0.45–0.85; P = .003; I2 = 43%) but not among the 6 double-blinded studies (OR 0.72, 95% CI 0.44–1.19; P = .20; I2 = 55%). We found a shorter duration of antibiotic use for VAP (mean difference −1.44, 95% CI −2.88 to −0.01; P = .048, I2 = 30%) in the probiotics group than in the control group, and the finding comes from just 2 studies. No statistically significant differences were found between the groups in terms of ICU mortality (OR 0.95, 95% CI 0.67–1.34; P = .77; I2 = 0%), ICU stay (mean difference –0.77, 95% CI –2.58 to 1.04; P = .40; I2 = 43%), duration of mechanical ventilation (mean difference –0.91, 95% CI –2.20 to 0.38; P = .17; I2 = 25%), or occurrence of diarrhea (OR 0.72, 95% CI 0.45–1.15; P = .17; I2 = 41%).CONCLUSIONS:The meta-analysis results indicated that the administration of probiotics significantly reduced the incidence of VAP. Furthermore, our findings need to be verified in large-scale, well-designed, randomized, multi-center trials. Full Article
led Circadian Clock-Controlled Drug Metabolism: Implications for Chronotherapeutics [Minireview] By dmd.aspetjournals.org Published On :: 2020-04-17T07:49:35-07:00 Dependence of drug metabolism on dosing time has long been recognized. However, only recently are the underlying mechanisms for circadian drug metabolism being clarified. Diurnal rhythmicity in expression of drug-metabolizing enzymes is believed to be a key factor determining circadian metabolism. Supporting the notion that biological rhythms are generated and maintained by the circadian clock, a number of diurnal enzymes are under the control of the circadian clock. In general, circadian clock genes generate and regulate diurnal rhythmicity in drug-metabolizing enzymes via transcriptional actions on one or two of three cis-elements (i.e., E-box, D-box, and Rev-erb response element or RAR-related orphan receptor response element). Additionally, cycling or clock-controlled nuclear receptors such as hepatocyte nuclear factor 4α and peroxisome proliferator–activated receptor are contributors to diurnal enzyme expression. These newly discovered mechanisms for each of the rhythmic enzymes are reviewed in this article. We also discuss how the rhythms of enzymes are translated to circadian pharmacokinetics and drug chronotoxicity, which has direct implications for chronotherapeutics. Our discussion is also extended to two diurnal transporters (P-glycoprotein and multidrug resistance-associated protein 2) that have an important role in drug absorption. Although the experimental evidence is lacking in metabolism-based chronoefficacy, circadian genes (e.g., Rev-erbα) as drug targets are shown to account for diurnal variability in drug efficacy. SIGNIFICANCE STATEMENT Significant progress has been made in understanding the molecular mechanisms for generation of diurnal rhythmicity in drug-metabolizing enzymes. In this article, we review the newly discovered mechanisms for each of the rhythmic enzymes and discuss how the rhythms of enzymes are translated to circadian pharmacokinetics and drug chronotoxicity, which has direct implications for chronotherapeutics. Full Article
led 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
led Acknowledgment of Ad Hoc Reviewers [Editorial] By cvi.asm.org Published On :: 2017-12-05T08:00:30-08:00 Full Article
led Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an By cvi.asm.org Published On :: 2017-12-05T08:00:30-08:00 Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 108 CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 109 CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 108-CFU standard dose (n = 50) or a ≥2 x 109-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.) Full Article
led Risk of MS relapse after yellow fever vaccination: A self-controlled case series By nn.neurology.org Published On :: 2020-05-01T12:45:10-07:00 Objective To determine whether live-attenuated yellow fever vaccine (YFV) was associated with MS relapse, we evaluated the clinical courses of 23 patients in the year before and the year after immunization at the university hospital of Geneva, Switzerland. Methods This self-controlled retrospective cohort included adult patients with MS receiving YFV between 2014 and 2018 and defined the year before vaccination, the 3 months thereafter, and the 9 months following as the pre-exposure (PEP), exposure-risk (ERP), and postrisk (PRP) periods, respectively. The primary outcome was the relative incidence of relapse in the ERP vs the PEP. Secondary end points included the presence of new T2-weighted (T2) or T1-weighted gadolinium-positive (T1Gd+) MRI lesions. Results Of 23 patients with MS receiving YFV (20 relapsing MS and 3 primary progressive MS), 17 (74%) were women; mean age was 34 years (SD ±10); and 10 of 23 (40%) were treated with disease-modifying therapies (DMTs). Although 9 patients experienced 12 relapses in the PEP, only one experienced a relapse in the ERP; 3 other patients experienced one relapse each in the PRP. None of the 8 patients receiving natalizumab at the time of vaccination experienced relapse thereafter. In the PEP, ERP, and PRP, 18, 2, and 9 patients had new brain and/or spinal cord lesions on T2 or T1Gd + MRI, respectively. Conclusions In this cohort, YF vaccination was associated with neither an increase in MS relapse nor emergence of brain and/or spinal lesions. Further studies are warranted to confirm these findings. Classification of evidence This study provides Class IV evidence that for persons with MS, YFV may not increase relapse risk. Full Article