Notes

Copper-Catalyzed Conjugate Inclusion of Carbonyls while Carbanion Equal by way of Hydrazones.
To identify needs in a clinical decision support tool development by exploring how primary care providers currently collect and use family health history (FHH).

Survey questionnaires and semi-structured interviews were administered to a mix of primary and specialty care clinicians within the University of Utah Health system (40 surveys, 12 interviews).

Three key themes emerged regarding providers' collection and use of FHH (1) Strategies for collecting FHH vary by level of effort; (2) Documentation practices extend beyond the electronic health record's dedicated FHH module; and (3) Providers desire feedback from genetic services consultation and are uncertain how to refer patients to genetic services.

Study findings highlight the varying degrees of engagement that providers have with collecting FHH. Improving the integration of FHH into workflow, and providing decision support, as well as links and tools to help providers better utilize genetic counseling may improve patient care.
Study findings highlight the varying degrees of engagement that providers have with collecting FHH. Improving the integration of FHH into workflow, and providing decision support, as well as links and tools to help providers better utilize genetic counseling may improve patient care.To elucidate the pharmacological effects of Rho-associated coiled-coil containing protein kinase inhibitors (ROCK-is), ripasudil (Rip), Y27632, and KD025, on human orbital fatty tissue, the human orbital fibroblasts (HOFs) were three-dimensional (3D) cultured for 12 days. The effects of ROCK-is on the physical properties of the 3D-cultured HOF spheroids, including their sizes and physical stiffness, their adipogenesis by lipid staining, and the mRNA expression of adipogenesis-related genes, PPARγ and AP2, and extracellular matrix (ECM) including collagen (COL) 1, 4, and 6, and fibronectin were analyzed. A significant increase in the sizes, physical stiffness, lipid staining, and mRNA expression of adipogenesis-related genes, COL4 and COL6, and a decrease in COL1 expression were observed with adipogenesis (DIF+). In the presence of ROCK-is, such DIF+-induced effects were differently modulated as follows (1) the sizes were not affected or significantly enhanced by Rip, Y27632, or KD025, (2) the physical stiffness was significantly decreased in Rip and Y27632, but was substantially increased in KD025, (3) the lipid staining was further enhanced or significantly suppressed by Rip, Y27632, or KD025, and both PPARγ and AP2 expression were significantly downregulated or upregulated by KD025 or Rip, and (4) Rip upregulated the expression of COL4, Y27632 upregulated the expression of COL1, COL4, and COL6, and KD025 upregulated the expression of COL1 and COL4. This study indicates that ROCK-is significantly and differently modulate physical properties of the 3D HOF spheroids as well as their adipogenesis.The damaging effects of air pollution on the skin are becoming increasingly researched and the outcomes of this research are now a major influence in the selection and development of protective ingredients for skincare formulations. However, extensive research has not yet been conducted into the specific cellular defense systems that are being affected after exposure to such pollutants. Research investigating the affected systems is integral to the development of suitable interventions that are capable of augmenting the systems most impacted by air pollutant exposure. The following studies involved exposing primary human dermal fibroblasts to different concentrations of particulate matter and analyzing its effects on mitochondrial complex activity, nuclear factor erythroid 2-related factor 2 localization using immunocytochemistry and protein expression of electron transport chain complex proteins, sirtuin-1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) using western blotting. Particulate matter-induced alterations in both mitochondrial complex protein and activity, indicating oxidative stress, which was also complimented by increased expression of antioxidant proteins GSTP1/2 and SOD2. Particulate matter also seemed to modify expression of the proteins SIRT1 and PGC-1α which are heavily involved in the regulation of mitochondrial biogenesis and energy metabolism. Given the reported results indicating that particulate matter induces damage through oxidative stress and has a profound effect on mitochondrial homeostasis, interventions involving targeted mitochondrial antioxidants may help to minimize the damaging downstream effects of pollutant-induced oxidative stress originating from the mitochondria.Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The F508del and G542X are the most common mutations found in US patients, accounting for 86.4% and 4.6% of all mutations, respectively. The F508del causes deletion of the phenylalanine residue at position 508 and is associated with impaired CFTR protein folding. The G542X is a nonsense mutation that introduces a stop codon into the mRNA, thus preventing normal CFTR protein synthesis. Doxorubicin mw Here, we describe the generation of CFTRF508del / F508del and CFTRG542X / G542X lambs using CRISPR/Cas9 and somatic cell nuclear transfer (SCNT). First, we introduced either F508del or G542X mutations into sheep fetal fibroblasts that were subsequently used as nuclear donors for SCNT. The newborn CF lambs develop pathology similar to CFTR -/- sheep and CF patients. Moreover, tracheal epithelial cells from the CFTRF508del / F508del lambs responded to a human CFTR (hCFTR) potentiator and correctors, and those from CFTRG542X / G542X lambs showed modest restoration of CFTR function following inhibition of nonsense-mediated decay (NMD) and aminoglycoside antibiotic treatments. Thus, the phenotype and electrophysiology of these novel models represent an important advance for testing new CF therapeutics and gene therapy to improve the health of patients with this life-limiting disorder.Despite promising preclinical and clinical data demonstrating that immune agonist antibody immunotherapies (IAAs) such as αOX40 induce strong antitumor immune responses, clinical translation has been significantly hampered by the propensity of some IAAs to induce dose-limiting and sometimes life-threatening immunotoxicities such as cytokine release syndrome and hepatotoxicity. For example, in a recent study αOX40 was shown to induce significant liver damage in mice by inducing the pyroptosis of liver natural killer T cells (NKT) cells. Surprisingly; however, given these previous reports, αOX40 treatment in our hands did not induce NKT cell pyroptosis or liver damage. We investigated numerous potential confounding factors including age, sex, tumor burden, dosing strategy, and the gut microbiota, which could have explained this discrepancy with the previous study. In none of these experiments did we find that αOX40 induced any more than very mild inflammation in the liver. Our study therefore suggests that, preclinically, αOX40 is a safe and effective immunotherapy and further studies into the clinical benefit of αOX40 are warranted.As APS President-elect, I participated in the Williamsburg Retreat in 1989 to address the issue of keeping member societies in FASEB. The Retreat led to focusing on public affairs and reducing society dues. As APS President, I met with leadership of ASBMB to convince them to remain in the restructured FASEB. As the first elected President of the new FASEB in 1992, I organized member societies to participate in NIH Strategic Plan meeting to maintain the priority of funding of unsolicited investigator-initiated research instead of a top-down approach. A new Office for Policy Analysis and Research was established to pursue proactive public affairs activities and strategic thinking. In response to qualitative and quantitative threats to biomedical research funding, I worked with FASEB member societies and the Public Affairs office to mobilize letter-writing and a petition drive to the President and Members of US Congress, resulting in >20,000 signatures. This led to a 6.1% increase of FY94 funding, instead of a cut. When FASEB's annual meeting was changed to Experimental Biology (EB), I worked with EB to ensure the smooth transition. I organized Tang Prize Lectures which became the highly successful EB plenary lectures. My involvement with FASEB was helpful in the formation of NIBIB in 2001 and recruitment of BMES as a member society in 2008.A hallmark of endometriosis - a chronic debilitating condition whose causes are poorly understood - is neuronal innervation of lesions. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with endometriosis but also contribute to a pro-growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. The diverse array of contributions that neurons play in endometriosis indicate that it should be considered as a nerve-centric disease. This review is focused on the emerging field of exoneural biology and how it applies to the field of endometriosis, in particular the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the mechanisms of neuronal contribution to endometriosis, as well as their interactions with accompanying stromal and immune cells, will unearth novel disease-relevant pathways and targets, providing additional, more selective therapeutic horizons.Extracellular vesicles (EVs) are released by many different cell types throughout the body and play a role in a diverse range of biological processes. EVs circulating in blood as well as in other body fluids undergo dramatic alterations over an organism's lifespan that are only beginning to be elucidated. The exact nature of these changes is an area of active and intense investigation, but lacks clear consensus due to the substantial heterogeneity in EV subpopulations and insufficiencies in current technologies. Nonetheless, emerging evidence suggests that EVs regulate systemic aging as well as the pathophysiology of age-related diseases. Here, we review the current literature investigating EVs and aging with an emphasis on consequences for the maintenance of human healthspan. Intriguingly, the biological utility of EVs both in vitro and in vivo and across contexts depends on the states of the source cells or tissues. As such, EVs secreted by cells in an aged or pathological state may impose detrimental consequences on recipient cells, while EVs secreted by youthful or healthy cells may promote functional improvement. Thus, it is critical to understand both functions of EVs and tip the balance toward their beneficial effects as an antiaging intervention.The density of nerves in cancer is emerging as a relevant clinical parameter for patient survival. Nerves in the tumor microenvironment have been associated with poor survival and recurrence, particularly if involved in perineural invasion. However, usually only a few nerves inside a tumor are affected by perineural invasion, while most nerves are not. Mechanistic studies have shown nerve-secreted factors promote tumor growth and invasion thereby making tumors more aggressive. Therefore, the overall number of nerves in the tumor microenvironment should be more representative of the nerve-tumor biological interaction than perineural invasion. This review summarizes the available clinical information about nerve density as a measure of clinical outcome in cancer and explores the mechanisms underlying nerve density in cancer, specifically, neurogenesis, axonogenesis, and neurotropism.
Here's my website: https://www.selleckchem.com/products/Adriamycin.html