Regulatory reforms should focus on building up market competition, which indirectly forces state-owned enterprises to improve their operation toward efficiency.

This paper presents an analysis of business development programs (BDPs) based on a theoretical framework aimed at understanding the mixed effect of business training on entrepreneurs.

AN3401 - Using Microchip I2C EERAMs with MPLAB X and MPLAB Code Configurator

STAMFORD, CT – November 7, 2019 – HARMAN – a wholly-owned subsidiary of Samsung Electronics Co., Ltd., focused on connected technologies for automotive, consumer and enterprise markets, together with the 1,000 Dreams Fund (1DF), today announced the...

At HARMAN, we believe the future of the workplace is one where individuals can take time away from work to focus on their families and caregiving duties without sacrificing the ability to drive a successful career. Through our partnership with Path...

Mathematicians have come up with a way to explore strange 3D spaces that could be related to the shape of the universe

Investors in SkyBridge Capital asked for hundreds of millions of dollars back after the fund suffered a 23% loss in March when investments made by its debt-focused hedge fund managers soured, Anthony...

Extreme storms Hurricane Florence and Typhoon Mangkhut have caused destruction and taken lives across the globe this week, forcing millions to evacuate their homes

A dead whale found in the Philippines with 40 kilograms of plastic inside its body is the latest example of the problem of plastic pollution

How to use the Maillard reaction to make delicious dulce de leche – the ultimate comfort food when you are stuck indoors, says Sam Wong

Srinivisa Ramanujan’s ideas seemed to come from a parallel universe and mathematicians are still getting to grips with them today, say Ken Ono and Robert Schneider

Hyperconsumption adds to environmental destruction that brings people into contact with animal viruses that can spark pandemics. We have to avoid the temptation to rely on it to get us out, writes Graham Lawton

Many ancient monuments are claimed to be aligned to celestial phenomena, but we now have the first statistical evidence this is the case for the Egyptian pyramids

While most film and TV production around the world has shut down, one UK network has made a new drama series "Isolation Stories" about life under lockdown. Edward Baran reports.

Srinivisa Ramanujan’s ideas seemed to come from a parallel universe and mathematicians are still getting to grips with them today, say Ken Ono and Robert Schneider

Hyperconsumption adds to environmental destruction that brings people into contact with animal viruses that can spark pandemics. We have to avoid the temptation to rely on it to get us out, writes Graham Lawton

Many ancient monuments are claimed to be aligned to celestial phenomena, but we now have the first statistical evidence this is the case for the Egyptian pyramids

Title: Veramyst Treats Seasonal and Year-Round Allergies
Category: Health News
Created: 5/1/2007 2:00:00 AM
Last Editorial Review: 5/1/2007 12:00:00 AM

Title: Home Monitoring Program Improves Outcomes for Heart Patients
Category: Health News
Created: 5/2/2008 2:00:00 AM
Last Editorial Review: 5/2/2008 12:00:00 AM

Title: Educational Program Urges Parents to Immunize Kids
Category: Health News
Created: 4/27/2010 8:10:00 AM
Last Editorial Review: 4/27/2010 12:00:00 AM

Title: Studies Point to Reasons for Mammograms in 40s
Category: Health News
Created: 5/1/2012 11:00:00 AM
Last Editorial Review: 5/1/2012 12:00:00 AM

Title: School Programs Do Keep Some Kids From Smoking
Category: Health News
Created: 4/30/2013 10:35:00 AM
Last Editorial Review: 4/30/2013 12:00:00 AM

Title: Longer Wait for Mammogram After Benign Breast Biopsy May Be Warranted
Category: Health News
Created: 5/2/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Training Programs Protect Young Athletes From ACL Tears: Report
Category: Health News
Created: 4/28/2014 9:35:00 AM
Last Editorial Review: 4/28/2014 12:00:00 AM

Title: Trampolines Linked to More Than 1 Million ER Visits Over a Decade
Category: Health News
Created: 5/2/2014 12:35:00 PM
Last Editorial Review: 5/2/2014 12:00:00 AM

Title: C-Section Rates Drop Slightly With Hospital Review Program
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM

Title: Contraception Safety Program for Acne Drug Failing in Canada
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 12:00:00 AM

Title: Earlier Mammograms May Mean Less Need for Aggressive Treatments
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: Breast Cancer Prognosis May Be Worse If Diagnosis Follows 'Negative' Mammogram
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

JATS-Con is a conference for users of the Journal Article Tag Suite, that is, users of any of the "NLM DTDs" or NISO Z39.96. JATS-Con will take place on the NIH campus in Bethesda, Maryland on October 22 and 23, 2013.

The full program is now available, as are proceedings from previous years.

There is no charge for the conference; however, space is limited so registration is required.

You may also sign up for a pre-conference tutorial on October 21, 2013. Details are on the Tutorial Registration page.

Title: Tramadol vs. Codeine
Category: Medications
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 12/20/2019 12:00:00 AM

Title: Citalopram (Celexa)
Category: Medications
Created: 2/2/1999 12:00:00 AM
Last Editorial Review: 2/12/2020 12:00:00 AM

Title: Lexapro (escitalopram)
Category: Medications
Created: 3/16/2003 12:00:00 AM
Last Editorial Review: 2/24/2020 12:00:00 AM

Title: Obamacare May Have Boosted Use of Mammograms
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

ABSTRACT

Bacterial flagella are rotating nanomachines required for motility. Flagellar gene expression and protein secretion are coordinated for efficient flagellar biogenesis. Polar flagellates, unlike peritrichous bacteria, commonly order flagellar rod and hook gene transcription as a separate step after production of the MS ring, C ring, and flagellar type III secretion system (fT3SS) core proteins that form a competent fT3SS. Conserved regulatory mechanisms in diverse polar flagellates to create this polar flagellar transcriptional program have not been thoroughly assimilated. Using in silico and genetic analyses and our previous findings in Campylobacter jejuni as a foundation, we observed a large subset of Gram-negative bacteria with the FlhF/FlhG regulatory system for polar flagellation to possess flagellum-associated two-component signal transduction systems (TCSs). We present data supporting a general theme in polar flagellates whereby MS ring, rotor, and fT3SS proteins contribute to a regulatory checkpoint during polar flagellar biogenesis. We demonstrate that Vibrio cholerae and Pseudomonas aeruginosa require the formation of this regulatory checkpoint for the TCSs to directly activate subsequent rod and hook gene transcription, which are hallmarks of the polar flagellar transcriptional program. By reprogramming transcription in V. cholerae to more closely follow the peritrichous flagellar transcriptional program, we discovered a link between the polar flagellar transcription program and the activity of FlhF/FlhG flagellar biogenesis regulators in which the transcriptional program allows polar flagellates to continue to produce flagella for motility when FlhF or FlhG activity may be altered. Our findings integrate flagellar transcriptional and biogenesis regulatory processes involved in polar flagellation in many species.

IMPORTANCE Relative to peritrichous bacteria, polar flagellates possess regulatory systems that order flagellar gene transcription differently and produce flagella in specific numbers only at poles. How transcriptional and flagellar biogenesis regulatory systems are interlinked to promote the correct synthesis of polar flagella in diverse species has largely been unexplored. We found evidence for many Gram-negative polar flagellates encoding two-component signal transduction systems with activity linked to the formation of flagellar type III secretion systems to enable production of flagellar rod and hook proteins at a discrete, subsequent stage during flagellar assembly. This polar flagellar transcriptional program assists, in some manner, the FlhF/FlhG flagellar biogenesis regulatory system, which forms specific flagellation patterns in polar flagellates in maintaining flagellation and motility when activity of FlhF or FlhG might be altered. Our work provides insight into the multiple regulatory processes required for polar flagellation.

ABSTRACT

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris. These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans. Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to express translation initiation factor 1 (Tif1) with the variant amino acid that we had identified in C. auris, translation was inhibited but no programmed cell death phenotypes were observed. This surprising finding suggests divergence between these related fungal pathogens in their pathways of cellular responses to translation inhibition. From a therapeutic perspective, the chemical biology that we have uncovered reveals species-specific vulnerability in C. auris and identifies a promising target for development of new, mechanistically distinct antifungals in the battle against this emerging pathogen.

IMPORTANCE Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that C. auris is surprisingly sensitive to translation inhibition by a class of compounds known as rocaglates (also known as flavaglines). Despite the high level of conservation across fungi in their protein synthesis machinery, these compounds inhibited translation initiation and activated a cell death program in C. auris but not in its relative Candida albicans. Our findings highlight a surprising divergence across the cell death programs operating in Candida species and underscore the need to understand the specific biology of a pathogen in attempting to develop more-effective treatments against it.

On a single day in September, nearly 43,000 adults and children in the U.S. were living in emergency housing because of domestic violence.

BACKGROUND Pregnant patients from rural counties of Western North Carolina face additional barriers when accessing comprehensive perinatal substance use disorders care at Project CARA as compared to patients local to the program in Buncombe County. We hypothesized regional patients would be less engaged in care.

METHOD Using a retrospective cohort design, univariate analyses (², t-test; P < .05) compared patients' characteristics, engagement in care, and delivery outcomes. Engagement in care, the primary outcome, was operationalized as: attendance at expected, program-specific prenatal and postpartum visits, utilization of in-house counseling, community-based and/or inpatient substance use disorders treatment, and maternal urine drug screen at delivery negative for illicit substances.

RESULTS Regional patients (n = 324) were more likely than Buncombe County patients (n = 284) to have opioid [209 (64.5%) versus 162 (57.0%)] or amphetamine/methamphetamine use disorders (25 [7.7%] versus 13 [4.6%]), but less likely to have cannabis use (19 [5.9%] versus 38 [13.4%]; P = .009) and concurrent psychiatric disorders (214 [66.0%] versus 220 [77.5%]; P = .002). Engagement at postpartum visits was the significantly different outcome between patients (110/221 [49.8%] versus 146/226 [64.6%]; P = .002).

LIMITATIONS Outcomes were available for 66.8% of regional and 79.6% of Buncombe County patients of one program in one predominately white, non-Hispanic region of the state.

CONCLUSION Contrary to our hypothesis, regional and Buncombe County women engaged in prenatal care equally. However, a more formal transition into the postpartum period is needed, especially for regional women. A "hub-and-spokes" model that extends delivery of perinatal substance use disorders care into rural communities may be more effective for engagement retention.

Purpose of review

Diverse adverse events have been associated with administration of glatiramer acetate (GA), mainly local reactions at the injection site. Other, less frequent generalized reactions include isolated postinjection reactions and anaphylaxis, which may lead to discontinuation of GA.

Surgical procedures are performed in the United States in a wide variety of clinical settings and with variation in clinical outcomes. In May 2012, the Task Force for Children’s Surgical Care, an ad hoc multidisciplinary group comprising physicians representing specialties relevant to pediatric perioperative care, was convened to generate recommendations to optimize the delivery of children’s surgical care. This group generated a white paper detailing the consensus opinions of the involved experts. Following these initial recommendations, the American College of Surgeons (ACS), Children’s Hospital Association, and Task Force for Children’s Surgical Care, with input from all related perioperative specialties, developed and published specific and detailed resource and quality standards designed to improve children’s surgical care (https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification). In 2015, with the endorsement of the American Academy of Pediatrics (https://pediatrics.aappublications.org/content/135/6/e1538), the ACS established a pilot verification program. In January 2017, after completion of the pilot program, the ACS Children’s Surgery Verification Quality Improvement Program was officially launched. Verified sites are listed on the program Web site at https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification/centers, and more than 150 are interested in verification. This report provides an update on the ACS Children’s Surgery Verification Quality Improvement Program as it continues to evolve.

We describe an atypical pediatric case of immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, in which formation of spontaneous hematoma of the paraspinal muscles developed. Spontaneous or unprovoked hematomas rarely occur in IgAV. These manifestations have not been described specifically in the pediatric literature as coinciding with IgAV. These findings are alarming for nonaccidental trauma, particularly in a patient without underlying blood dyscrasia. Our objective for this report is to highlight the possible association of muscular hematoma formation with IgAV and to help providers consider this association when trauma and hemophilia has been ruled out.

Key Points