Antimicrobial Interventions to Reduce Listeria spp. Contamination on Shrimp

The effects of selected antimicrobials, applied singularly or in combination, and frozen or refrigerated storage conditions on the survival of Listeria spp. on inoculated shrimp was evaluated in this study. A combination of 0.5% CPC (Cetylpyridinium Chloride) with a water wash at room temperature and freezing of the shrimp at -22.3 degrees C was the only treatment that had a significant antimicrobial effect on the Listeria spp. Antimicrobial effects and the mode of action of PEF (Pulsed Electric Field) and CPC on Listeria cells were evaluated in detailed studies. PEF in 0.1% sodium chloride had a bacterostatic effect toward Listeria spp. during refrigerated storage, but no immediate or bacteriostatic effect was caused by freezing the samples. A concentration of 1% sodium chloride reduced the Listeria spp. population after freezing by 1.1 log; however, the pungent chlorine odor that was generated during treatment might cause discomfort for employees in shrimp processing facilities. Also, chlorine might cause corrosion of metal surfaces of processing equipment. There was no difference in the antimicrobial effects on the survival of Listeria spp. by PEF between the exposure times of 1 or 2 min, as well as in the sodium chloride concentrations of 0.1 and 0.5%. PEF treatment in the presence of 0.1% sodium chloride is recommended. A solution of 0.5% CPC effectively inhibited all of the strains of Listeria spp. in the cell suspensions. A treatment of 0.5% CPC combined with PEF treatment in a sodium chloride concentration of 0.1% caused a delayed effect on the Listeria spp. after 2 d of refrigerated storage. After 2 d of frozen storage, the formation of ice crystals was decreased in the number of Listeria spp. when contaminated samples were treated with water. The results indicated chemicals (e.g. CPC and NaCl) might protect Listeria spp. from the formation of ice crystals. TEM (Transmission Electron Microscopy) micrographs revealed that cell membranes were damaged by PEF treatment and that cells were ruptured by CPC treatment. A maximum reduction of 2.76 log10 CFU/g of Listeria spp. on shrimp was achieved by a combination of PEFCPC

Nanoparticle conversion to biofilms: in vitro demonstration using serum-derived mineralo-organic nanoparticles

Aims: Mineralo-organic nanoparticles (NPs) detected in biological fluids have been described as precursors of physiological and pathological calcifications in the body. Our main objective was to examine the early stages of mineral NP formation in body fluids. Materials & methods: A nanomaterial approach based on atomic force microscopy, dynamic light scattering, electron microscopy and spectroscopy was used. Results: The mineral particles, which contain the serum proteins albumin and fetuin-A, initially precipitate in the form of round amorphous NPs that gradually grow in size, aggregate and coalesce to form crystalline mineral films similar to the structures observed in calcified human arteries. Conclusion: Our study reveals the early stages of particle formation and provides a platform to analyze the role(s) of mineralo-organic NPs in human tissues

Detection and characterization of mineralo-organic nanoparticles in human kidneys

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as well as within the cytoplasm of tubule-delineating cells, and consist of polycrystalline calcium phosphate similar to the mineral found in bones and ectopic calcifications. The kidney mineral nanoparticles contain several serum proteins that inhibit ectopic calcification in body fluids, including albumin, fetuin-A, and apolipoprotein A1. Since the mineralo-organic nanoparticles are found not only within calcified deposits but also in areas devoid of microscopic calcifications, our observations indicate that the nanoparticles may represent precursors of calcification and renal stones in humans

Dense Cranial Electroacupuncture Stimulation for Major Depressive Disorder—A Single-Blind, Randomized, Controlled Study

BACKGROUND: Previous studies suggest that electroacupuncture possesses therapeutic benefits for depressive disorders. The purpose of this study was to determine whether dense cranial electroacupuncture stimulation (DCEAS) could enhance the antidepressant efficacy in the early phase of selective serotonin reuptake inhibitor (SSRI) treatment of major depressive disorder (MDD). METHODS: In this single-blind, randomized, controlled study, patients with MDD were randomly assigned to 9-session DCEAS or noninvasive electroacupuncture (n-EA) control procedure in combination with fluoxetine (FLX) for 3 weeks. Clinical outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), Clinical Global Impression-severity (CGI-S), and Self-rating Depression Scale (SDS) as well as the response and remission rates. RESULTS: Seventy-three patients were randomly assigned to n-EA (n = 35) and DCEAS (n = 38), of whom 34 in n-EA and 36 in DCEAS group were analyzed. DCEAS-treated patients displayed a significantly greater reduction from baseline in HAMD-17 scores at Day 3 through Day 21 and in SDS scores at Day 3 and Day 21 compared to patients receiving n-EA. DCEAS intervention also produced a higher rate of clinically significant response compared to n-EA procedure (19.4% (7/36) vs. 8.8% (3/34)). The incidence of adverse events was similar in the two groups. CONCLUSIONS: DCEAS is a safe and effective intervention that augments the antidepressant efficacy. It can be considered as an additional therapy in the early phase of SSRI treatment of depressed patients. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN88008690

Altered cofactor regulation with disease-associated p97/VCP mutations

Dominant mutations in p97/VCP (valosin-containing protein) cause a rare multisystem degenerative disease with varied phenotypes that include inclusion body myopathy, Paget’s disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. p97 disease mutants have altered N-domain conformations, elevated ATPase activity, and altered cofactor association. We have now discovered a previously unidentified disease-relevant functional property of p97 by identifying how the cofactors p37 and p47 regulate p97 ATPase activity. We define p37 as, to our knowledge, the first known p97-activating cofactor, which enhances the catalytic efficiency (k_(cat)/K_m) of p97 by 11-fold. Whereas both p37 and p47 decrease the K_m of ATP in p97, p37 increases the k_(cat) of p97. In contrast, regulation by p47 is biphasic, with decreased k_(cat) at low levels but increased k_(cat) at higher levels. By deleting a region of p47 that lacks homology to p37 (amino acids 69–92), we changed p47 from an inhibitory cofactor to an activating cofactor, similar to p37. Our data suggest that cofactors regulate p97 ATPase activity by binding to the N domain. Induced conformation changes affect ADP/ATP binding at the D1 domain, which in turn controls ATPase cycling. Most importantly, we found that the D2 domain of disease mutants failed to be activated by p37 or p47. Our results show that cofactors play a critical role in controlling p97 ATPase activity, and suggest that lack of cofactor-regulated communication may contribute to p97-associated disease pathogenesis

Effectiveness of BNT162b2 and CoronaVac vaccinations against mortality and severe complications after SARS-CoV-2 Omicron BA.2 infection: a case–control study

Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case–control study to evaluate the risk of severe complications and mortality following 1–3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6–92.3) and 74.8% (72.5–76.9) in those aged ≥65, 87.6% (81.4–91.8) and 80.7% (72.8–86.3) in those aged 50–64, 86.6% (71.0–93.8) and 82.7% (56.5–93.1) in those aged 18–50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6–87.3) and 58.9% (50.3–66.1) in those aged ≥65, 83.0% (69.6–90.5) and 67.1% (47.1–79.6) in those aged 50–64, 78.3% (60.8–88.0) and 77.8% (49.6–90.2) in those aged 18–50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5–98.9) for BNT162b2 and 95.5% (93.7–96.8) for CoronaVac against mortality, 90.8% (83.4–94.9) and 88.0% (80.8–92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose

Functionalization of Styrenes by Copper‐Catalyzed Borylation/ ortho‐Cyanation and Silver‐Catalyzed Annulation Processes

An efficient two‐step method for the assembly of indanone derivatives starting from a simple vinyl arene has been developed. The sequence first involves addition of bis(pinacolato)diboron (B2pin2) and N‐cyano‐N‐phenyl‐p‐methylbenzenesulfonamide (NCTS) to a broad range of styrenes by utilizing IMesCuCl as catalyst. This step simultaneously accomplishes hydroboration of the alkene and ortho cyanation of the benzene unit. The products thus obtained are further functionalized by a AgNO3/Selectfluor‐mediated coupling of the BPin and cyano functionalities to annulate a new five‐membered ring. This combined two‐step sequence provides a versatile method for the site‐selective derivatization of a broad range of vinyl arene substrates.A Cu and Ag sequence: The bis‐functionalization of styrenes is accomplished through a copper‐catalyzed process that enables hydroboration of the alkene and regioselective ortho cyanation of the arene. The resulting adducts are converted, by a radical cyclization process, into a cyclopentanone unit fused to the original aromatic ring. Together, these methods allow efficient cyclopentannulation of a broad range of styrene derivatives.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115938/1/anie_201507303_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115938/2/12683_ftp.pd

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting