Πέμπτη 17 Δεκεμβρίου 2020

Ophthalmology Clinics

COVID-19 and the Eye: A Comprehensive Review of the Literature
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A Review and Update on Surgical Management of Intraocular Lens Dislocation
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Updates in the Management of Corneal Ectasia
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Review: Optimizing DMEK Technique, 2018-2020
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Recent Advances in Pediatric Endothelial Keratoplasty
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Recent Updates in Femtosecond Laser-assisted Cataract Surgery
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Alpha-Gal Syndrome in Ophthalmology and Medicine: Erratum
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients

Alexandros G.Sfakianakis shared this article with you from Inoreader
Μέσω Cancers

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Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients

Cancers doi: 10.3390/cancers12123821

Authors: Hanna A. Zielinska Carl S. Daly Ahmad Alghamdi Amit Bahl Muhammed Sohail Paul White Sarah R. Dean Jeff M. P. Holly Claire M. Perks

Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan–Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.

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Plasma proteomic data can contain personally identifiable, sensitive information and incidental findings [Research]

Alexandros G.Sfakianakis shared this article with you from Inoreader

The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

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Cardiac and sudden death after chronic total occlusion percutaneous coronary intervention: Prognostic role of the target vessel

Alexandros G.Sfakianakis shared this article with you from Inoreader

Abstract

Background

The role of the target vessel in percutaneous revascularization of chronic total occlusion (CTO) is unclear.

Objective

We sought to assess the long‐term results of percutaneous coronary intervention (PCI) for CTO lesions in each coronary artery and to investigate the impact of successful revascularization and previous myocardial infarction (MI) in the territory of the target vessel.

Methods and Results

Cohort observational study on 1,124 patients who have undergone CTO PCI attempt: 371 on left anterior descending artery (LAD), 485 right coronary artery, and 268 left circumflex. Patients were further stratified by successfully revascularized and not‐revascularized CTO (CTO‐NR). Vessels affected by a previous MI were defined as infarct‐related artery (IRA). The primary endpoint was cardiac death; the secondary endpoint was the combined rate of sudden cardiac‐death and sustained ventricular‐arrhythmias (SCD/SVAs). Propensity score‐matching was performed to evaluate LAD versus NON‐LAD CTO. Up to 12‐year follow‐up, the clinical benefit associated with successful PCI was consistent across the three groups. CTO‐NR had the greatest association with cardiac death and SCD/SVAs in each coronary artery and in IRA‐CTO patients.

Conclusions

Unsuccessful percutaneous CTO revascularization was associated with lower cardiac survival and freedom from SCD/SVAs, irrespective of the vessel treated. This result was mainly driven by patients with an IRA CTO.

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Is Candida auris sexual?

Alexandros G.Sfakianakis shared this article with you from Inoreader

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by Zoe K. Ross, Alexander Lorenz

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The Synergistic Effect of Hyperthermia and Chemotherapy in Magnetite Nanomedicine-Based Lung Cancer Treatment

Alexandros G.Sfakianakis shared this article with you from Inoreader

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A conscious choice: Is it ethical to aim for unconsciousness at the end of life?

Alexandros G.Sfakianakis shared this article with you from Inoreader
Μέσω Bioethics

Abstract

One of the most commonly referenced ethical principles when it comes to the management of dying patients is the doctrine of double effect (DDE). The DDE affirms that it is acceptable to cause side effects (e.g. respiratory depression) as a consequence of symptom‐focused treatment. Much discussion of the ethics of end of life care focuses on the question of whether actions (or omissions) would hasten (or cause) death, and whether that is permissible. However, there is a separate question about the permissibility of hastening or causing unconsciousness in dying patients. Some authors have argued that the DDE would not permit end of life care that directly aims to render the patient unconscious. The claim is that consciousness is an objective human good and therefore doctors should not intentionally (and permanently) suppress it. Three types of end of life care (EOLC) practices will be explored in this article. The first is symptom‐based management (e.g. analgesia); the second is proportional terminal sedation as a means of relieving suffering (also referred to as palliative sedation or continuous deep sedation); and finally, deliberate and rapid sedation to unconsciousness until death (a practice we call terminal anaesthesia in this paper). After examining the common arguments for the various types of symptom‐based management and sedation, we apply the DDE to the latter two types of EOLC practices. We argue that aiming at unconsciousness, contrary to some claims, can be morally good or at least morally neutral in some dying patients.

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The role of gene dosage in budding yeast centrosome scaling and spontaneous diploidization

Alexandros G.Sfakianakis shared this article with you from Inoreader

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by Jingjing Chen, Zhiyong Xiong, Danny E. Miller, Zulin Yu, Scott McCroskey, William D. Bradford, Ann M. Cavanaugh, Sue L. Jaspersen

Ploidy is the number of whole sets of chromosomes in a species. Ploidy is typically a stable cellular feature that is critical for survival. Polyploidization is a route recognized to increase gene dosage, improve fitness under stressful conditions and promote evolutionary diversity. However, the mechanism of regulation and maintenance of ploidy is not well characterized. Here, we examine the spontaneous diploidization associated with mutations in components of the Saccharomyces cerevisiae centrosome, known as the spindle pole body (SPB). Although SPB mutants are associated with defects in spindle formation, we show that two copies of the mutant in a haploid yeast favors diploidization in some cases, leading us to speculate that the increased gene dosage in diploids 'rescues' SPB duplication defects, allowing cells to successfully propagate with a stable diploid karyotype. This copy number-based rescue is linked to SPB scaling: certain SPB subcomplexes do not scale or only minimally scale with ploidy. We hypothesize that lesions in structures with incompatible allometries such as the centrosome may drive changes such as whole genome duplication, which have shaped the evolutionary landscape of many eukaryotes.
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Nationwide germline whole genome sequencing of 198 consecutive pediatric cancer patients reveals a high frequency of cancer prone syndromes

Alexandros G.Sfakianakis shared this article with you from Inoreader

journal.pgen.1009231.g002&size=inline

by Anna Byrjalsen, Thomas V. O. Hansen, Ulrik K. Stoltze, Mana M. Mehrjouy, Nanna Moeller Barnkob, Lisa L. Hjalgrim, René Mathiasen, Charlotte K. Lautrup, Pernille A. Gregersen, Henrik Hasle, Peder S. Wehner, Ruta Tuckuviene, Peter Wad Sackett, Adrian O. Laspiur, Maria Rossing, Rasmus L. Marvig, Niels Tommerup, Tina Elisabeth Olsen, David Scheie, Ramneek G upta, Anne–Marie Gerdes, Kjeld Schmiegelow, Karin Wadt

PURPOSE: Historically, cancer predisposition syndromes (CPSs) were rarely established for children with cancer. This nationwide, population-based study investigated how frequently children with cancer had or were likely to have a CPS.METHODS: Children (0–17 years) in Denmark with newly diagnosed cancer were invited to participate in whole-genome sequencing of germline DNA. Suspicion of CPS was assessed according to Jongmans'/McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) criteria and familial cancer diagnoses were verified using population-based registries. RESULTS: 198 of 235 (84.3%) eligible patients participated, of whom 94/198 (47.5%) carried pathogenic variants (PVs) in a CPS gene or had clinical features indicating CPS. Twenty-nine of 198 (14.6%) patients harbored a CPS, of whom 21/198 (10.6%) harbored a childhood-onset and 9/198 (4.5%) an adult-onset CPS. In addition, 23/198 (11.6%) patients carried a PV associated with biallelic CPS. Seven of the 54 (12.9%) patients carried two or more variants in different CPS genes. Seventy of 198 (35.4%) patients fulfilled the Jongmans' and/or MIPOGG criteria indicating an underlying CPS, including two of the 9 (22.2%) patients with an adult-onset CPS versus 18 of the 21 (85.7%) patients with a childhood-onset CPS (p = 0.0022), eight of the additional 23 (34.8%) patients with a heterozygous PV associated with biallelic CPS, and 42 patients without PVs. Children with a central nervous system (CNS) tumor had family members with CNS tumors more frequently than patients with other cancers (11/44, p = 0.04), but 42 of 44 (95.5%) cases did not have a PV in a CPS gene. CONCLUSION: These results demonstrate the value of systematically screening pediatric cancer patients for CPSs and indicate that a higher proportion of childhood cancers may be linked to predisposing germline variants than previously supposed.
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The Staphylococcus aureus phosphoproteome reveals new targets of Stk1

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Staphylococcus aureus is a major cause of infections worldwide and infection results in a variety of diseases. As of no surprise, protein phosphorylation is an important game player in signaling cascades and has been shown to be involved in S. aureus virulence. Albeit long neglected, eukaryotic-type serine/threonine kinases in S. aureus have been implicated in this complex signaling cascades. Due to the sub-stoichio metric nature of protein phosphorylation and a lack of suitable analysis tools, the knowledge of these cascades is however, to date, still limited.

Here, were apply an optimized protocol for efficient phosphopeptide enrichment via Fe3+-IMAC followed by LC-MS/MS to get a better understanding of the impact of protein phosphorylation on the complex signaling networks involved in pathogenicity. By profiling a serine/threonine kinase and phosphatase mutant from a methicillin-resistant S. aureus mutant library, we generated the most comprehensive phosphoproteome dataset of S. aureus to date, aiding a better understanding of signaling in bacteria. With the identification of 3800 class I p-sites we were able to increase the number of identifications by more than 21 times compared to recent literature. In addition, we were able to identify 74 downstream targets of the only reported eukaryotic-type Ser/Thr kinase of the S. aureus strain USA300, Stk1. This work allowed an extensive analysis of the bacterial phosphoproteome and indicates that Ser/Thr kinase signaling is far more abundant than previously anticipated in S. aureus.

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Identification of novel serological autoantibodies in Takayasu arteritis patients using HuProt arrays [Research]

Alexandros G.Sfakianakis shared this article with you from Inoreader

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To identify novel autoantibodies of Takayasu arteritis (TAK) using HuProt array-based approach. A two-phase approach was adopted. In Phase I, serum samples collected from 40 TAK patients, 15 autoimmune disease patients, and 20 healthy subjects were screened to identify TAK-specific autoantibodies using human protein (HuProt) arrays. In Phase II, the identified candidate autoantibodies were validated with TAK-focused arrays us ing an additional cohort comprised of 109 TAK patients, 110 autoimmune disease patients, and 96 healthy subjects. Subsequently, the TAK-specific autoantibodies validated in Phase II were further confirmed using Western blot analysis. We identified and validated eight autoantibodies as potential TAK-specific diagnostic biomarkers, including anti-SPATA7, -QDPR, -SLC25A2, -PRH2, -DIXDC1, -IL17RB, -ZFAND4, and -NOLC1 antibodies, with AUC of 0.803, 0.801, 0.780, 0.696, 0.695, 0.678, 0.635 and 0.613, respectively. SPATA7 could distinguish TAK from healthy and disease controls with 73.4% sensitivity at 85.4% specificity, while QDPR showed 71.6% sensitivity at 86.4% specificity. SLC25A22 showed the highest sensitivity of 80.7%, but at lower specificity of 67.0%. In addition, PRH2, IL17RB and NOLC1 showed good specificities of 88.3%, 85.9% and 86.9%, respectively, but at lower sensitivities (<50%). Finally, DIXDC1 and ZFAND4 showed moderate performance as compared with the other autoantib odies. Using a decision tree model, we could reach a specificity of 94.2% with AUC of 0.843, a significantly improved performance as compared to that by each individual biomarker. The performance of three autoantibodies, namely anti-SPATA7, -QDPR and -PRH2, were successfully confirmed with Western blot analysis. Using this two-phase strategy, we identified and validated eight novel autoantibodies as TAK–specific biomarker candidates, three of which could be readily adopted in a clinical setting.

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In Vivo Confocal Microscopy and Anterior Segment Optical Coherence Tomography Analysis of the Microcystic Keratitis

Alexandros G.Sfakianakis shared this article with you from Inoreader

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Purpose. To describe the findings of in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) in a case of bilateral acute microcystic epitheliopathy after daily soft contact lens wear. Methods. IVCM and AS-OCT were used in the course of the bilateral epitheliopathy of a 23-year-old patient at the acute stage of the disease and at recovery after four days of treatment. The images were analyzed and compared. Results. On AS-OCT of the right eye, general hyperreflectivity and the increased thickness of the central corneal epithelium to 150 μm with numerous hyporeflective small, oval cysts were revealed and resolved completely at day 4 after diagnosis and treatment. AS-OCT scans of the left eye revealed oval shaped, hyperreflective material within the corneal epithelium. IVCM of both eyes showed numerous microcysts of different sizes filled with hyperreflective material mostly within superficial epithelial layers. Epithelial cells showed a polymorphism along with disruption of a cytoarchitecture. Basal epithelial cells and anterior stroma showed inflammatory changes. Posterior corneal stroma and endothelium presented normal morphology. Conclusions. Microcystic keratitis appeared as localized microcystic inflammation of epithelium on AS-OCT, which was confirmed by IVCM. Both IVCM and AS-OCT are helpful diagnostic instruments in case of cystic inflammation of corneal epithelium.
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