IMPORTANCE: There is a need for validated clinical end points that are reliably able to quantify potential therapeutic effects of future treatments targeting age-related macular degeneration (AMD) ...before the onset of serious visual impairment. OBJECTIVE: To assess the reliability and discriminatory power of 5 simple chart-based visual function (VF) tests as potential measures for clinical trial end points with regulatory and patient-access intention in intermediate AMD (iAMD). DESIGN, SETTING, AND PARTICIPANTS: This international noninterventional study took place at 18 tertiary ophthalmology departments across Europe. Participants were recruited between April 2018 and March 2020 and were identified during routine clinical review. Participants with no AMD and early AMD were recruited from hospital staff, friends, and family of participants with AMD and via referrals from community ophthalmologists and optometrists. The repeatability and discriminatory power of 5 simple chart-based assessments of VF (best-corrected visual acuity BCVA, low-luminance visual acuity LLVA, Moorfields Acuity Test MAT, Pelli-Robson Contrast Sensitivity CS, and International Reading Speed Test IReST) were assessed in a repeated-measures design. VF assessments were performed on day 0 and day 14. Participants with early AMD, iAMD, late AMD, and no AMD were recruited. MAIN OUTCOMES AND MEASURES: Intraclass correlation coefficients (ICCs) and Bland-Altman 95% limits of agreement (LoA) were computed to assess repeatability. Area under the receiver operating characteristic curves (AUCs) determined the discriminatory ability of all measures to classify individuals as having no AMD or iAMD and to differentiate iAMD from its neighboring disease states. RESULTS: A total of 301 participants (mean SD age, 71 7 years; 187 female participants 62.1%) were included in the study. Thirty-four participants (11.3%) had early AMD, 168 (55.8%) had iAMD, 43 (14.3%) had late AMD, and 56 (18.6%) had no AMD. ICCs for all VF measures ranged between 0.88 and 0.96 when all participants were considered, indicating good to excellent repeatability. All measures displayed excellent discrimination between iAMD and late AMD (AUC, 0.92-0.99). Early AMD was indistinguishable from iAMD on all measures (AUC, 0.54-0.64). CS afforded the best discrimination between no AMD and iAMD (AUC, 0.77). Under the same conditions, BCVA, LLVA, and MAT were fair discriminators (AUC, 0.69-0.71), and IReST had poor discrimination (AUC, 0.57-0.61). CONCLUSIONS AND RELEVANCE: BCVA, LLVA, MAT, CS, and IReST had adequate repeatability in this multicenter, multiexaminer setting but limited power to discriminate between no AMD and iAMD. The prognostic power of these variables to predict conversion from iAMD to late AMD is being examined in the ongoing longitudinal part of the MACUSTAR study.
The duration and protectiveness of antibodies against SARS-CoV-2 in infected subjects are still uncertain; nonetheless, anti-S-specific antibodies can contribute to protective immunity against new ...infections. It has been described that the level of antibodies produced in COVID-19 is related to the severity of symptoms, and the majority of the humoral response studies have been conducted in hospitalized patients who have been, then, followed over time. However, about 80% of SARS-CoV-2 infections in unvaccinated people are mild to asymptomatic, and this percentage reaches more than 95% in vaccinated individuals. Therefore, understanding the long-term dynamics of the antibody responses in this predominant part of the COVID-19-affected population is essential. In this study, we followed a cohort of individuals with mild COVID-19 who did not require hospitalization. We collected blood samples at sequential times after the SARS-CoV-2-positive qRT-PCR result. From 65 recruited patients, 50 had detectable antibodies at screening. Anti-SARS-CoV-2 IgM levels peaked around two weeks post-COVID-19 diagnostics, becoming undetectable after 65 days. IgG levels reached a peak in approximately one month and remained detectable for more than one year. In contrast to the levels of anti-SARS-CoV-2, antibody neutralization potency indexes persisted over time. In this study, humoral responses in mild COVID-19 patients persisted for more than one year. This is an important long-term follow-up study that includes responses from COVID-19 patients before and after vaccination, a scenery that has become increasingly difficult to evaluate due to the growing vaccination of the world human population.
The compounds mPTACoCl4 (1, mPTA = N‐methyl‐1,3,5‐triaza‐7‐phosphaadamantane cation), CoCl(H2O)(DION)2BF4 (2, DION = 1,10‐phenanthroline‐5,6‐dione), Zn(DION)2Cl2 (3) and ZnCl(κO‐PTA=O)(DION)BF4 (4) ...were synthesized by reaction of CoCl2 with mPTAI or DION and ZnCl2 with DION or 1,3,5‐triaza‐7‐phosphaadamantane‐7‐oxide (PTA=O) and DION, respectively. All complexes are water soluble and have been characterized by IR, far‐IR, 1H, 13C and 31P{1H} NMR spectroscopy, ESI‐MS, elemental analyses and single‐crystal X‐ray diffraction structural analysis (for 1). They were screened against the human tumour cell lines HCT116, HepG2 and MCF7. Complexes 2 and 3 exhibit the highest in vitro cytotoxicity and show lower cytotoxic activities in normal human fibroblast cell line than in HCT116 tumour cell line, which demonstrates their slight specificity for this type of tumour cell.
Cobalt and zinc compounds with 1,3,5‐triaza‐7‐phosphaadamantane (PTA) derivatives and/or 1,10‐phenanthroline‐5,6‐dione (DION) have been synthesized, characterized and screened against several human tumour cell lines. The DION‐containing compounds exhibit specificity for the human fibroblast.
The very high antiproliferative activity of Co(Cl)(H
2
O)(phendione)
2
BF
4
(phendione is 1,10-phenanthroline-5,6-dione) against three human tumor cell lines (half-maximal inhibitory concentration ...below 1 μM) and its slight selectivity for the colorectal tumor cell line compared with healthy human fibroblasts led us to explore the mechanisms of action underlying this promising antitumor potential. As previously shown by our group, this complex induces cell cycle arrest in S phase and subsequent cell death by apoptosis and it also reduces the expression of proteins typically upregulated in tumors. In the present work, we demonstrate that Co(Cl)(phendione)
2
(H
2
O)BF
4
(1) does not reduce the viability of nontumorigenic breast epithelial cells by more than 85 % at 1 μM, (2) promotes the upregulation of proapoptotic Bax and cell-cycle-related p21, and (3) induces release of lactate dehydrogenase, which is partially reversed by ursodeoxycholic acid. DNA interaction studies were performed to uncover the genotoxicity of the complex and demonstrate that even though it displays
K
b
(± standard error of the mean) of (3.48 ± 0.03) × 10
5
M
−1
and is able to produce double-strand breaks in a concentration-dependent manner, it does not exert any clastogenic effect ex vivo, ruling out DNA as a major cellular target for the complex. Steady-state and time-resolved fluorescence spectroscopy studies are indicative of a strong and specific interaction of the complex with human serum albumin, involving one binding site, at a distance of approximately 1.5 nm for the Trp214 indole side chain with log
K
b
~4.7, thus suggesting that this complex can be efficiently transported by albumin in the blood plasma.
This work studies the surface characteristics, antimicrobial activity, and aging effect of plasma-pretreated polyamide 6,6 (PA66) fabrics coated with silver nanoparticles (AgNPs), aiming to identify ...the optimum size of nanosilver exhibiting antibacterial properties suitable for the manufacture of hospital textiles. The release of bactericidal Ag+ ions from a 10, 20, 40, 60, and 100 nm AgNPs-coated PA66 surface was a function of the particles’ size, number, and aging. Plasma pretreatment promoted both ionic and covalent interactions between AgNPs and the formed oxygen species on the fibers, favoring the deposition of smaller-diameter AgNPs that consequently showed better immediate and durable antimicrobial effects against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. Surprisingly, after 30 days of aging, a comparable bacterial growth inhibition was achieved for all of the fibers treated with AgNPs <100 nm in size. The Ag+ in the coatings also favored the electrostatic stabilization of the plasma-induced functional groups on the PA66 surface, thereby retarding the aging process. At the same time, the size-related ratio (Ag+/Ag0) of the AgNPs between 40 and 60 nm allowed for the controlled release of Ag+ rather than bulk silver. Overall, the results suggest that instead of reducing the size of the AgNPs, which is associated with higher toxicity, similar long-term effects can be achieved with larger NPs (40–60 nm), even in lower concentrations. Because the antimicrobial efficiency of AgNPs larger than 30 nm is mainly ruled by the release of Ag+ over time and not by the size and number of the AgNPs, this parameter is crucial for the development of efficient antimicrobial coatings on plasma-treated surfaces and contributes to the safety and durability of clothing used in clinical settings.
Many processes involved in the pathogenesis of atherosclerosis result in modifications of the extracellular matrix. These changes not only determine the mechanical stability of atherosclerotic ...lesions but can directly or indirectly influence further development of the lesions. The purpose of the present study was to compare the matrix composition of human carotid plaques from symptomatic patients with those obtained from patients without symptoms. Furthermore, matrix changes related to age were studied.
Thirty atherosclerotic carotid plaques were removed by endarterectomy from 27 patients and divided into 2 groups on the basis of the presence of ipsilateral symptoms. The plaques were homogenized, and the total levels of the major components of the extracellular matrix were determined.
Plaques associated with symptoms were characterized by increased levels of elastin (1.58+/-0.46 versus 1.24+/-0.40 mg/g wet wt; P=0.03) and decreased levels of hydroxyapatite (45.1+/-46.3 versus 131.4+/-111.7 mg/g wet wt; P=0.02) compared with asymptomatic plaques. The increase in elastin in plaques from symptomatic patients was due to elevated levels of an intermediate-size fraction, as determined by liquid chromatography. Collagen and sulfated glycosaminoglycans were present in equal amounts in both groups. Elastin content in carotid plaques decreased with age.
Carotid plaques from symptomatic patients have lower levels of hydroxyapatite than those from asymptomatic patients. The present study also raises the possibility that non-cross-linked forms of elastin, increased in plaques associated with symptoms, could be a marker of plaque vulnerability and/or directly induce harmful cellular activities or increase lipoprotein retention in the vascular wall.
Abstract
For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. ...As the field of genomics grows and more data become available, new modes of display are required to accommodate new technologies. New features released this past year include a Hi-C heatmap display, a phased family trio display for VCF files, and various track visualization improvements. Striving to keep data up-to-date, new updates to gene annotations include GENCODE Genes, NCBI RefSeq Genes, and Ensembl Genes. New data tracks added for human and mouse genomes include the ENCODE registry of candidate cis-regulatory elements, promoters from the Eukaryotic Promoter Database, and NCBI RefSeq Select and Matched Annotation from NCBI and EMBL-EBI (MANE). Within weeks of learning about the outbreak of coronavirus, UCSC released a genome browser, with detailed annotation tracks, for the SARS-CoV-2 RNA reference assembly.
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