Title: Do Your Knees Crackle and Pop?
Category: Health News
Created: 5/5/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: Health Tip: Create a Sick-Day Plan for Diabetes
Category: Health News
Created: 5/5/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: Sugary Drinks More Affordable Across the Globe
Category: Health News
Created: 5/4/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: Scientists Pinpoint Dozens of Genes That Increase Risk of Depression
Category: Health News
Created: 4/27/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: Opioid Crisis Means More Newborns With Hepatitis C, But Few Get Tested
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: The Other Opioid Crisis: Shortages at U.S. Hospitals
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: FDA Cracks Down on Dangerous E-Cig Liquids That Resemble Cookies, Candy
Category: Health News
Created: 5/1/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM

Title: Home Gym: The Benefits of a Cross-Country Ski Machine
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: VA Doctors Prescribing Unnecessary Antibiotics, Study Says
Category: Health News
Created: 4/26/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: 4 Strategies to Cope With a Food Craving
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Measles Case Leads to Quarantine of Cruise Ship in St. Lucia
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: There May Be Antidote for Ocean's Most Venomous Creature
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: 'Microbiome' May Be Key to Autism Symptoms
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: A Heart-Healthy Prescription for America's Food System
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: Was Dyslexia the Secret to Leonardo da Vinci's Greatness?
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: In COVID Crisis, Nearly Half of People in Some U.S. States Are Going Hungry
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: Coronavirus Crisis Has Fewer Kids Getting Needed Vaccines
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

Title: Out-of-Hospital Cardiac Arrests On the Rise During COVID-19 Crisis
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk?
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM

Title: CRISPR Used Inside Person's Body For First Time
Category: Health News
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

Title: Will a Jolt of Java Get Your Creative Juices Flowing?
Category: Health News
Created: 3/9/2020 12:00:00 AM
Last Editorial Review: 3/9/2020 12:00:00 AM

Title: Screen Time for Tiniest Tots Linked to Autism-Like Symptoms
Category: Health News
Created: 4/20/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM

Title: AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early Death
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM

In a sign of the times and things to come, in-person cardiovascular society meetings pivot to virtual events.

Three physicians describe their impressions of video-based evaluations and things to watch out for.

Americans are reporting high levels of emotional distress from the coronavirus pandemic – levels that some experts warn may lead to national mental health crisis.

The PMC Canada manuscript submission system was released on April 28, 2010. The system will enable researchers funded by the Canadian Institutes of Health Research to deposit their peer-reviewed research publications, in compliance with CIHR's Policy on Access to Research Outputs.

NIH-supported scientists have made over 300,000 author manuscripts available in PMC. Now NIH is making these papers accessible to the public in a format that will allow robust text analyses.

You can download the PMC collection of NIH-supported author manuscripts as a package in either XML or plain-text format at ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/manuscript/. The collection encompasses all NIH manuscripts posted to PMC that were published in July 2008 or later. While the public can access the manuscripts’ full text and accompanying figures, tables, and multimedia via the PMC website, the newly available XML and plain-text files include full text only. In addition to text mining, the files may be used consistent with the principles of fair use under copyright law.

Please note that these author manuscript files are not part of the PMC Open Access Subset.

The NIH Office of Extramural Research developed this resource to increase the impact of NIH funding. Through this collection, scientists will be able to analyze these manuscripts, further apply NIH research findings, and generate new discoveries.

For more information, please visit the PMC author manuscript collection webpage.

Title: Doctors Describe First Drone Delivery of Diabetes Meds to Patient
Category: Health News
Created: 3/30/2020 12:00:00 AM
Last Editorial Review: 3/31/2020 12:00:00 AM

Title: Herpes Virus Yields Up Genetic Secrets
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Prescription-Strength Steroid Creams Sold Over-the-Counter Can Be Dangerous
Category: Health News
Created: 1/23/2020 12:00:00 AM
Last Editorial Review: 1/24/2020 12:00:00 AM

Title: AHA News: These Stroke Survivors May Not Be Prescribed Enough Blood Pressure Meds
Category: Health News
Created: 2/21/2020 12:00:00 AM
Last Editorial Review: 2/24/2020 12:00:00 AM

Title: Crafting With Dry Pasta, Play-Doh Safe for Kids With Gluten Sensitivity: Study
Category: Health News
Created: 2/4/2020 12:00:00 AM
Last Editorial Review: 2/5/2020 12:00:00 AM

Title: Many Car Crash Deaths Involve Alcohol Levels Below Legal Limit: Study
Category: Health News
Created: 3/16/2020 12:00:00 AM
Last Editorial Review: 3/17/2020 12:00:00 AM

Title: Ride-Sharing Services Tied to Rise in Car Crashes
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

Title: AHA News: Stroke Survivors Might Need Better Screening for Depression
Category: Health News
Created: 2/12/2020 12:00:00 AM
Last Editorial Review: 2/13/2020 12:00:00 AM

Title: Spring Time Change Tied to More Fatal Car Crashes
Category: Health News
Created: 1/30/2020 12:00:00 AM
Last Editorial Review: 1/31/2020 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.

The invertebrate trace fossils Selenichnites rossendalensis and Crescentichnus tesiltus are recorded and described from the Middle Jurassic Gristhorpe Member of the Cloughton Formation of the Cleveland Basin. This is the first record of these ichnospecies from the basin and now completes the occurrence of these and other traces assumed to have been made by limulids from all three non-marine formations of the Ravenscar Group.

Commonly used model teeth are so far uniform in color and hardness. There is no discrimination between enamel and dentin part of a tooth. This condition makes it difficult to train a preparation technique, which is adapted to real tooth substance. The aim of this study was to design and establish a 3D printed tooth with different layers for enamel and dentin for education in crown preparation. A printable tooth with different layers for enamel and dentin was designed, and all 38 fourth-year dental students in the first clinical course in prosthodontics and 30 experienced dentists were trained during a voluntary hands-on course in 2019. Prior to the study, the students had used standard model teeth and real-teeth models in their preclinical education. They had experience in caries removal and preparation on real patients. The perceived benefits of the 3D printed tooth were evaluated by a questionnaire. All individuals in both groups completed the questionnaire, for a 100% response rate. The results showed that the printed tooth was given an overall mean grade of 2.3 (students) and 2.0 (experts) on a scale from 1=excellent to 5=poor. The difference in hardness between the dentin and enamel layer was given a mean of 2.4 (students and experts) and the difference in color a 1.7 (students) and 1.8 (experts). The tooth model with the prepared tooth illustrating an ideal preparation was graded 1.6 (students and experts). In this study, the students had the opportunity to learn a correct crown preparation on a printed tooth with different material properties for enamel and dentin. The learning effect with this tooth model was rated as good on the questionnaire by both students and expert dentists.

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.

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R^–/–) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by ²H/¹³C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^MyeLDLR^–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXR^MyeLDLR^–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXR^MyeLDLR^–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.

Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

ABSTRACT

Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Here, we show that myositis induced by Ross River virus (RRV) infection is driven by CD11b^hi Ly6C^hi inflammatory monocytes and followed by the establishment of a CD11b^hi Ly6C^lo CX₃CR1⁺ macrophage population in the muscle upon recovery. Selective modulation of CD11b^hi Ly6C^hi monocyte migration to infected muscle using immune-modifying microparticles (IMP) reduced disease score, tissue damage, and inflammation and promoted the accumulation of CX₃CR1⁺ macrophages, enhancing recovery and resolution. Here, we detail the role of immune pathology, describing a poorly characterized muscle macrophage subset as part of the dynamics of alphavirus-induced myositis and tissue recovery and identify IMP as an effective immunomodulatory approach. Given the lack of specific treatments available for alphavirus-induced pathologies, this study highlights a therapeutic potential for simple immune modulation by IMP in infected individuals in the event of large alphavirus outbreaks.

IMPORTANCE Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX₃CR1⁺ macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX₃CR1⁺ macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.

ABSTRACT

Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of RNA viruses, we questioned whether obesity could also influence influenza virus population diversity. Here, we show that minor variants rapidly emerge in obese mice. The variants exhibit increased viral replication, resulting in enhanced virulence in wild-type mice. The increased diversity of the viral population correlated with decreased type I interferon responses, and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral response exhibited in obesity permits the emergence of a more virulent influenza virus population. This is not unique to obese mice. Obesity-derived normal human bronchial epithelial (NHBE) cells also showed decreased interferon responses and increased viral replication, suggesting that viral diversity also was impacted in this increasing population.

IMPORTANCE Currently, 50% of the adult population worldwide is overweight or obese. In these studies, we demonstrate that obesity not only enhances the severity of influenza infection but also impacts viral diversity. The altered microenvironment associated with obesity supports a more diverse viral quasispecies and affords the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts. This is likely due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise.