The no-retina-touch technique: vitrectomy and platelet-rich plasma in the treatment of lamellar macular hole. New insights into pathogenesis.

Purpose: To explore the use of autologous platelet-rich plasma (PRP) as a potential therapeutic adjuvant strategy for treating degenerative lamellar macular holes (LMHs).

Design: A prospective interventional case series.

Methods: Seven consecutive patients (8 eyes) with a diagnosis of LMH underwent a pars-plana vitrectomy with PRP injection under air tamponade.

Platelet rich plasma for primary macular hole: A case series.

Objective: To evaluate the anatomical and functional macular results and rate of complications following surgical treatment of primary macular hole (MH) with autologous platelet rich plasma (a-PRP) use.

Design: retrospective, interventional, non-randomized case series.

Partecipants And Methods: A cohort of 9 consecutive patients from January 1, 2019 to August 31, 2021 who underwent vitrectomy with a-PRP use for primary MH were included.

Platelet concentrates in macular hole surgery. A journey through the labyrinth of terminology, preparation, and application: a comprehensive review.

The surgical management of macular holes is undergoing continuous evolution, with recent focus on the utilization of platelet concentrates as a promising adjunctive intervention. Currently, they present a valid surgical approach for achieving anatomical and functional success with a non-inferiority comparably to the alternative surgical techniques. Nonetheless, the utilization of varied platelet concentrates terminologies, coupled with the lack of standardization in their preparation methodologies, engenders both lexical confusion and challenges in comparing scientific studies published up until now.

Macula-Off Retinal Detachment with Refractory Macular Hole Previously Closed with Autologous Platelet-Rich Plasma: A Case Report.

The purpose of this report was to present a case of a refractory full-thickness macular hole (FTMH) complicated with recurrent retinal detachment (RD) previously treated with an autologous platelet-rich plasma (aPRP) plug. A 65-year-old male patient presented to our department with a FTMH, RD, and a giant retinal break. Preoperative best corrected visual acuity (BCVA) was 1.

A Model for Predictive Maintenance Based on Asset Administration Shell.

Maintenance is one of the most important aspects in industrial and production environments. Predictive maintenance is an approach that aims to schedule maintenance tasks based on historical data in order to avoid machine failures and reduce the costs due to unnecessary maintenance actions. Approaches for the implementation of a maintenance solution often differ depending on the kind of data to be analyzed and on the techniques and models adopted for the failure forecasts and for maintenance decision-making.

Discovery and Lead Optimization of Atropisomer D1 Agonists with Reduced Desensitization.

The discovery of D1 subtype-selective agonists with drug-like properties has been an enduring challenge for the greater part of 40 years. All known D1-selective agonists are catecholamines that bring about receptor desensitization and undergo rapid metabolism, thus limiting their utility as a therapeutic for chronic illness such as schizophrenia and Parkinson's disease. Our high-throughput screening efforts on D1 yielded a single non-catecholamine hit PF-4211 (6) that was developed into a series of potent D1 receptor agonist leads with high oral bioavailability and CNS penetration.

Quantitative Translational Analysis of Brain Kynurenic Acid Modulation via Irreversible Kynurenine Aminotransferase II Inhibition.

Kynurenic acid (KYNA) plays a significant role in maintaining normal brain function, and abnormalities in KYNA levels have been associated with various central nervous system disorders. Confirmation of its causality in human diseases requires safe and effective modulation of central KYNA levels in the clinic. The kynurenine aminotransferases (KAT) II enzyme represents an attractive target for pharmacologic modulation of central KYNA levels; however, KAT II and KYNA turnover kinetics, which could contribute to the duration of pharmacologic effect, have not been reported.

Impaired β-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor.

Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40 years as a therapeutic strategy for neurologic and psychiatric diseases due to the fundamental role of D1Rs in motor function, reward processing, and cognition. All known D1R-selective agonists are catechols, which are rapidly metabolized and desensitize the D1R after prolonged exposure, reducing agonist response. As such, drug-like selective D1R agonists have remained elusive.

Dopamine D1 receptor-agonist interactions: A mutagenesis and homology modeling study.

The dopamine D1 receptor is a G protein-coupled receptor that regulates intracellular signaling via agonist activation. Although the number of solved GPCR X-ray structures has been steadily increasing, still no structure of the D1 receptor exists. We have used site-directed mutagenesis of 12 orthosteric vicinity residues of possible importance to G protein-coupled activation to examine the function of prototypical orthosteric D1 agonists and partial agonists.

PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency.

The structure-based design, synthesis, and biological evaluation of a new pyrazole series of irreversible KAT II inhibitors are described herein. The modification of the inhibitor scaffold of 1 and 2 from a dihydroquinolinone core to a tetrahydropyrazolopyridinone core led to discovery of a new series of potent KAT II inhibitors with excellent physicochemical properties. Compound 20 is the most potent and lipophilically efficient of these new pyrazole analogs, with a k(inact)/K(i) value of 112,000 M(-1)s(-1) and lipophilic efficiency (LipE) of 8.

Structure-Based Design of Irreversible Human KAT II Inhibitors: Discovery of New Potency-Enhancing Interactions.

A series of aryl hydroxamates recently have been disclosed as irreversible inhibitors of kynurenine amino transferase II (KAT II), an enzyme that may play a role in schizophrenia and other psychiatric and neurological disorders. The utilization of structure-activity relationships (SAR) in conjunction with X-ray crystallography led to the discovery of hydroxamate 4, a disubstituted analogue that has a significant potency enhancement due to a novel interaction with KAT II. The use of k inact/K i to assess potency was critical for understanding the SAR in this series and for identifying compounds with improved pharmacodynamic profiles.

Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia.

Kynurenine aminotransferase (KAT) II has been identified as a potential new target for the treatment of cognitive impairment associated with schizophrenia and other psychiatric disorders. Following a high-throughput screen, cyclic hydroxamic acid PF-04859989 was identified as a potent and selective inhibitor of human and rat KAT II. An X-ray crystal structure and (13)C NMR studies of PF-04859989 bound to KAT II have demonstrated that this compound forms a covalent adduct with the enzyme cofactor, pyridoxal phosphate (PLP), in the active site.

PF-03475952: a potent and neutralizing fully human anti-CD44 antibody for therapeutic applications in inflammatory diseases.

Introduction: CD44 is a cell adhesion molecule believed to play a critical role in T cell and monocyte infiltration in the inflammatory process. The reduction of CD44 expression or its ability to properly interact with its key ligand, hyaluronic acid (HA), inhibits migration and subsequent activation of cells within sites of inflammation. CD44-deficient mice exhibit decreased disease in a mouse arthritis model.

Genetic ablation of the src kinase p59fynT exacerbates pulmonary inflammation in an allergic mouse model.

p59fynT is a protein tyrosine kinase in the src family that has been associated with and believed to function in the signaling of many receptors, including the T-cell receptor. A role for the kinase in antigen-driven pulmonary inflammation was examined using mice whose p59fynT gene had been genetically ablated. FynKO mice that were sensitized to ovalbumin exhibited a marked increase in bronchoalveolar lavage eosinophils and cytokines, including interleukin (IL)-4 and IL-5, relative to wild-type mice in response to antigen aerosol exposure.

[Anesthesiologic and surgical problems in adenotonsillectomy in pediatric patients. Our current trend].

Aim: To verify, in dissection adenotonsillectomy (AT) performed in Rose position under general anaesthesia with oro-tracheal intubation, the following: 1) the ability of tramadol to produce an effective intra- and postoperative analgesia without any considerable side effects or interferences with the normal post-surgical course of the operation; 2) the possibility of obtaining, thanks to mivacurium, a myoresolution closer both to surgical times of the operation and to the necessity of a fast recovering of the pharyngo-laryngeal reflexes.

Experimental Design: A perspective and retrospective clinical study.

Setting: University clinic department (operating room and facility).

[Malformation processes in the middle ear. Branchio-oto-renal syndrome (BOR)].

The present report concerns a case of Branchio-Oto-Renal (BOR) dysplasia. The syndrome is an autosomal dominant inherited disorder characterized by external ear malformations, branchial fistulas, conductive mixed or sensorineural hearing loss and renal anomalies of varying severity. The types of abnormalities that may be present are numerous and often difficult to identify preoperatively, despite modern imaging techniques.