This story is published in a content partnership with POLITICO. It was originally reported by Myah Ward on politico.com on May 7, 2020.Melinda Gates on Thursday gave the Trump administration low marks for its handling of the coronavirus pandemic, adding that more money is needed for testing and vaccine development in the United States and across the world.Gates – co-chairman of the Bill & Melinda Gates Foundation, which has donated billions of dollars to health research – gave the…

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NEW YORK – Building on a busy year of new automotive technology introductions, HARMAN, the premium global audio, visual, infotainment and enterprise automation group (NYSE:HAR), will have a strong presence at the 2015 New York International Auto Show. From the company’s Clari-Fi™ digital music restoration technology to its next-generation QuantumLogic™ Surround Sound – HARMAN technology and solutions will be showcased in a host of new vehicles debuting at the show, highlighting HARMAN’s longstanding automotive partnerships and unmatched industry–leading innovations.

ABSTRACT

Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Our data indicated that GML significantly reduced body weight and visceral fat deposition, improved hyperlipidemia and hepatic lipid metabolism, and ameliorated glucose homeostasis and inflammation in HFD-fed mice. Importantly, GML modulated HFD-induced gut microbiota dysbiosis and selectively increased the abundance of Bifidobacterium pseudolongum. Antibiotic treatment abolished all the GML-mediated metabolic improvements. A multiomics (microbiome, metabolome, and transcriptome) association study showed that GML significantly modulated glycerophospholipid metabolism, and the abundance of Bifidobacterium pseudolongum strongly correlated with the metabolites and genes that participated in glycerophospholipid metabolism. Our results indicated that GML may be provided for obesity prevention by targeting the gut microbiota and regulating glycerophospholipid metabolism.

Cinnamaldehyde (Cin), a bioactive cinnamon essential oil from traditional Chinese medicine herb Cinnamomum cassia, has been reported to have multipharmacological activities including anti-inflammation. However, its role and molecular mechanism of anti-inflammatory activity in musculoskeletal tissues remains unclear. Here, we first investigated the effects and molecular mechanisms of Cin in human synoviocyte cells. Then in vivo therapeutic effect of Cin on collagen-induced arthritis (CIA) also studied. Cell Counting Kit ‎CCK-8 assay was performed to evaluate the cell cytotoxicity. Proinflammatory cytokine expression was evaluated using quantitative polymerase chain reaction and ELISA. Protein expression was measured by western blotting. The in vivo effect of Cin (75 mg/kg per day) was evaluated in rats with CIA by gavage administration. Disease progression was assessed by clinical scoring, radiographic, and histologic examinations. Cin significantly inhibited interleukin (IL)-1β–induced IL-6, IL-8, and tumor necrosis factor-α release from human synoviocyte cells. The molecular analysis revealed that Cin impaired IL-6–induced activation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1), and STAT3 signaling pathway by inhibiting the phosphorylation of JAK2, STAT1, and STAT3, without affecting NF-B pathway. Cin reduced collagen-induced swollen paw volume of arthritic rats. The anti-inflammation effects of Cin were associated with decreased severity of arthritis, joint swelling, and reduced bone erosion and destruction. Furthermore, serum IL-6 level was decreased when Cin administered therapeutically to CIA rats. Cin suppresses IL-1β–induced inflammation in synoviocytes through the JAK/STAT pathway and alleviated collagen-induced arthritis in rats. These data indicated that Cin might be a potential traditional Chinese medicine–derived, disease-modifying, antirheumatic herbal drug.

Sickle cell disease (SCD) is associated with overactive bladder (OAB). Detrusor overactivity, a component of OAB, is present in an SCD mouse, but the molecular mechanisms for this condition are not well-defined. We hypothesize that nitric oxide (NO)/ ras homolog gene family (Rho) A/Rho-associated kinase (ROCK) dysregulation is a mechanism for detrusor overactivity and that NO-releasing nanoparticles (NO-nps), a novel NO delivery system, may serve to treat this condition. Male adult SCD transgenic, combined endothelial NO synthases (eNOSs) and neuronal NOS (nNOS) gene-deficient (dNOS^–/–), and wild-type (WT) mice were used. Empty nanoparticle or NO-np was injected into the bladder, followed by cystometric studies. The expression levels of phosphorylated eNOS (Ser-1177), protein kinase B (Akt) (Ser-473), nNOS (Ser-1412), and myosin phosphatase target subunit 1 (MYPT1) (Thr-696) were assessed in the bladder. SCD and dNOS^–/– mice had a greater (P < 0.05) number of voiding and nonvoiding contractions compared with WT mice, and they were normalized by NO-np treatment. eNOS (Ser-1177) and AKT (Ser-473) phosphorylation were decreased (P < 0.05) in the bladder of SCD compared with WT mice and reversed by NO-np. Phosphorylated MYPT1, a marker of the RhoA/ROCK pathway, was increased (P < 0.05) in the bladder of SCD mice compared with WT and reversed by NO-np. nNOS phosphorylation on positive (Ser-1412) regulatory site was decreased (P < 0.05) in the bladder of SCD mice compared with WT and was not affected by NO-np. NO-nps did not affect any of the measured parameters in WT mice. In conclusion, dysregulation of NO and RhoA/ROCK pathways is associated with detrusor overactivity in SCD mice; NO-np reverses these molecular derangements in the bladder and decreases detrusor overactivity.

Vitamin D deficiency has been associated with increased incidence of diabetes, both in humans and in animal models. In addition, an association between vitamin D receptor (VDR) gene polymorphisms and diabetes has also been described. However, the involvement of VDR in the development of diabetes, specifically in pancreatic β-cells, has not been elucidated yet. Here, we aimed to study the role of VDR in β-cells in the pathophysiology of diabetes. Our results indicate that Vdr expression was modulated by glucose in healthy islets and decreased in islets from both type 1 diabetes and type 2 diabetes mouse models. In addition, transgenic mice overexpressing VDR in β-cells were protected against streptozotocin-induced diabetes and presented a preserved β-cell mass and a reduction in islet inflammation. Altogether, these results suggest that sustained VDR levels in β-cells may preserve β-cell mass and β-cell function and protect against diabetes.

Maintenance of the proteome, ensuring the proper locations, proper conformations, appropriate concentrations, etc., is essential to preserve the health of an organism in the face of environmental insults, infectious diseases, and the challenges associated with aging. Maintaining the proteome is even more difficult in the background of inherited mutations that render a given protein and others handled by the same proteostasis machinery misfolding prone and/or aggregation prone. Maintenance of the proteome or maintaining proteostasis requires the orchestration of protein synthesis, folding, trafficking, and degradation by way of highly conserved, interacting, and competitive proteostasis pathways. Each subcellular compartment has a unique proteostasis network compromising common and specialized proteostasis maintenance pathways. Stress-responsive signaling pathways detect the misfolding and/or aggregation of proteins in specific subcellular compartments using stress sensors and respond by generating an active transcription factor. Subsequent transcriptional programs up-regulate proteostasis network capacity (i.e., ability to fold and degrade proteins in that compartment). Stress-responsive signaling pathways can also be linked by way of signaling cascades to nontranscriptional means to reestablish proteostasis (e.g., by translational attenuation). Proteostasis is also strongly influenced by the inherent kinetics and thermodynamics of the folding, misfolding, and aggregation of individual proteins, and these sequence-based attributes in combination with proteostasis network capacity together influence proteostasis. In this review, we will focus on the growing body of evidence that proteostasis deficits leading to human pathology can be reversed by pharmacologic adaptation of proteostasis network capacity through stress-responsive signaling pathway activation. The power of this approach will be exemplified by focusing on the ATF6 arm of the unfolded protein response stress responsive-signaling pathway that regulates proteostasis network capacity of the secretory pathway.

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More than 56 million people in the United States live in areas with dentist shortages. Dental therapy is a proven solution that has helped increase access to care. Dental therapists are midlevel providers who deliver preventive and routine restorative treatment at schools, nursing homes, and veterans homes to people who would otherwise struggle to get access to care.

From : Communities>>Regulatory Open Forum
This message was posted by a user wishing to remain anonymous Hello, Does anyone know how long FDA's EUA process takes for approval compared to a 510k.  EUA seems to ask a lot of the same information that a 510k requests so not clear on what the benefits are or if it's worthwhile.  I assume you will eventually have to achieve traditional market clearance at some point. Any insight would be most appreciated. Thank you.

From : Communities>>Regulatory Open Forum
Hello, The EUA is much faster than the 510(k) process.  However, the EUA intended uses are only authorized during the state of emergency.  Once the state of emergency ends so does your authorization for the EUA intended uses.  The 510(k) clearance is permanent and authorizes the product with its cleared intended uses, to be put into interstate commerce. Hope that helps. ------------------------------ William Coulston PMP, MS, RAC Quality & Regulatory Manager San Antonio TX United States -------- [More]

From : Communities>>Regulatory Open Forum
Yes, you will need to achieve a 510(k) clearance after the emergency use has been officially ended by the FDA as William mentions.  Much of the information is the same, but the review process is intended to be expedited.  If you want to continue selling the product in the United States after the emergency use, you should really submit a 510(k) now; while the virus issue may continue for a few months it will take a few months for 510(k) clearance.  And if you have an EUA Approval this really is not [More]

April 27, 2020 – As the COVID-19 pandemic continues, the Food and Drug Administration (FDA) must balance safeguarding public health with the desire for timely product reviews. Staff members at the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research are working diligently to keep all of these balls in […]

By now, it is obvious to everyone seeking to understand the United States’ response to the novel coronavirus (officially SARS-CoV-2) that there were massive failures of judgment and inaction in January, February, and even March of this year. While mistakes are inevitable in the face of such a massive and rapidly evolving domestic and global…

Israelis voted in two Knesset elections in 2019, and a third will now follow in early 2020. Meanwhile, Attorney General Avichai Mandelblit announced the indictment of Prime Minister Benjamin Netanyahu, escalating the legal drama surrounding the prime minister. The task of forming a new coalition may be just as difficult after the third election as…

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