Background: Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS).
Materials And Methods: This retrospective analysis included 247 Dara-R MM patients treated with EloPd.
Objectives: Oligoarticular psoriatic arthritis (PsA) is frequent but rarely studied. The objective was to assess the efficacy of apremilast in early oligoarticular PsA.
Methods: FOREMOST (NCT03747939) was a phase 4 multicentre, randomised, double-blind, placebo-controlled trial.
It was a Lucky Strike to be working with Eraldo Antonini on hemoglobin and myoglobin when Jeffries Wyman arrived in Rome in 1961. I found myself connected with a number of creative scientists when the concept of allosteric control was conceived and gifted to the life science community. In retrospect, this was a demonstration of the skill and imagination of a few intelligent scientists that I happened to be close to.
View Article and Find Full Text PDFThe Corona Virus Disease of 2019 (COVID-19) pandemic has upset the students' daily routine, forcing them at first into a sudden transition to distance learning and then to a return to school modelled on the basis of infection containment measures. The present research involved 157 students from schools in central Italy with a mean age of 13.58 years old to investigate the affective impact of the pandemic on the school experience and its components (recess, oral testing, relationships with classmates, and relationship pupils-teachers).
View Article and Find Full Text PDFThe funneled energy landscape theory suggests that the folding pathway of homologous proteins should converge at the late stages of folding. In this respect, proteins displaying a broad energy landscape for folding are particularly instructive, allowing inferring both the early, intermediate and late stages of folding. In this paper we explore the folding mechanisms of human frataxin, an essential mitochondrial protein linked to the neurodegenerative disorder Friedreich's ataxia.
View Article and Find Full Text PDFAllostery arises when a ligand-induced change in shape of a binding site of a protein is coupled to a tertiary/quaternary conformational change with a consequent modulation of functional properties. The two-state allosteric model of Monod, Wyman and Changeux [J. Mol.
View Article and Find Full Text PDFIntroduction: Obstructive Sleep Apnea Syndrome (OSAS) is a relevant public health problem; dentists can play an important role in screening patients with sleep disorders by using validated tools and referring patients to a specialist, thereby promoting an interdisciplinary approach. The aim of the study is to identify if the OSAS severity, measured by the apnea-hypopnea index (AHI), and some anthropometric measurements are associated with the Friedman Tongue Position (FTP) within a population with dysmetabolic comorbidities.
Materials And Methods: A questionnaire containing information about clinical data including height, weight, Body Mass Index (BMI), neck circumference, waist circumference, hip circumference and FTP was administered.
"Can order spring from Chaos?" is the title of an extensive Report on Italian science published by NATURE on 12 May 1983 and written by Robert Walgate, the Chief European Correspondent. It is a twenty pages complete paper touching all aspects of the struggle of Italian scientists to work in the "curious amalgam of ingenuity and muddle, a reflection of the political system". (Nature, 1983; 303: 109-128).
View Article and Find Full Text PDFFront Mol Biosci
June 2022
The study of the mechanisms whereby proteins achieve their native functionally competent conformation has been a key issue in molecular biosciences over the last 6 decades. Nevertheless, there are several debated issues and open problems concerning some aspects of this fundamental problem. By considering the emerging complexity of the so-called "native state," we attempt hereby to propose a personal account on some of the key topics in the field, ranging from the relationships between misfolding and diseases to the significance of protein disorder.
View Article and Find Full Text PDFThe combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers.
View Article and Find Full Text PDFInt J Environ Res Public Health
May 2022
Introduction: OSAS is an emerging public health problem. Early diagnosis in adults with comorbidities is the gold standard to avoid complications caused by a late diagnosis. The aim of the study, part of the SLeeP@SA project, was to identify within a population with dysmetabolic comorbidities the association of occlusal clinical signs, defined by orthodontic parameters, and of the anthropometric phenotype, with the severity of OSAS.
View Article and Find Full Text PDFIntroduction: PALACE 1, 2, and 3 were phase 3 studies aimed to evaluate apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior treatment with conventional disease-modifying anti-rheumatic drugs and/or biologics. The pooled analysis reported here further characterized the clinical outcomes associated with long-term apremilast exposure in patients failing to achieve ≥ 20% improvement in the American College of Rheumatology response criteria (ACR20) at Week 104.
Methods: Patients randomized to apremilast 30 mg twice daily at baseline and classified as ACR20 non-responders (ACR20NRs) or ACR20 responders (ACR20Rs) at Week 104 were included.
Seventy years ago, we learned from Chris Anfinsen that the stereochemical code necessary to fold a protein is embedded into its amino acid sequence. In water, protein morphogenesis is a spontaneous reversible process leading from an ensemble of disordered structures to the ordered functionally competent protein; conforming to Aristotle's definition of substance, the synolon of matter and form. The overall process of folding is generally consistent with a two state transition between the native and the denatured protein: not only the denatured state is an ensemble of several structures, but also the native protein populates distinct functionally relevant conformational (sub)states.
View Article and Find Full Text PDFBackground: Omalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last decade have demonstrated its efficacy in other Immunoglobulin E related diseases, its use in such conditions is off-label.
Objective: This study aimed to assess the effectiveness of long-term therapy with Omalizumab in patients with persistent severe allergic rhinitis and inadequately controlled severe asthma.
Although more than 75% of the proteome is composed of multidomain proteins, current knowledge of protein folding is based primarily on studies of isolated domains. In this work, we describe the folding mechanism of a multidomain tandem construct comprising two distinct covalently bound PDZ domains belonging to a protein called Whirlin, a scaffolding protein of the hearing apparatus. In particular, via a synergy between NMR and kinetic experiments, we demonstrate the presence of a misfolded intermediate that competes with productive folding.
View Article and Find Full Text PDFThe novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic, threatening global public health. In the current paper, we describe our successful treatment of one COVID-19 pneumonia patient case with high mortality risk factors. Our experience underlines the importance of the use of a multidisciplinary therapeutic approach in order to achieve a favorable clinical outcome.
View Article and Find Full Text PDFMuch of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins.
View Article and Find Full Text PDFInt J Environ Res Public Health
March 2020
Small-scale or artisanal mining, using gold-mercury amalgamation to extract gold from ore, is a significant source of exposure for the workers and nearby populations. Few studies on hair mercury (Hg) have been conducted in Africa despite the fact that Africa has several gold deposits. No studies have been conducted in Eritrea that is one of the emerging gold producing countries in Africa.
View Article and Find Full Text PDFInt J Environ Res Public Health
February 2020
The purpose of this study was to evaluate the prevalence of position-dependent obstructive sleep apnea (POSA) in elderly patients (≥65 years old). Adult (range 19-65 years old) and elderly patients were also compared in order to show differences in the incidence of POSA between these two groups of patients. A prospective bi-center study was performed between January 2018 and May 2019.
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