Pushing the Limits of MALDI-TOF Mass Spectrometry: Beyond Fungal Species Identification

Matrix assisted laser desorption ionization time of flight (MALDI–TOF) is a powerful analytical tool that has revolutionized microbial identification. Routinely used for bacterial identification, MALDI-TOF has recently been applied to both yeast and filamentous fungi, confirming its pivotal role in the rapid and reliable diagnosis of infections. Subspecies-level identification holds an important role in epidemiological investigations aimed at tracing virulent or drug resistant clones. This review focuses on present and future applications of this versatile tool in the clinical mycology laboratory

From the Intersection of Food-Borne Zoonoses and EU Green Policies to an In-Embryo One Health Financial Model

The European Union (EU) adopts the One Health (OH) approach, based on the relationships between human, animal, and environmental health. OH concerns a multitude of aspects, some of which are discussed here. OH overlaps the European Green Deal plan and its relaunched Farm to Fork Strategy, which aims at spreading organic farms adopting the circular economy, in order to improve human health through both better environmental conditions and healthier food. Nevertheless, zoonoses cause sanitary cost in terms of infected farm personnel, lower productivity, and lower fertility of infected farm animals. In such scenarios, the decreased breeding yield and the lower income induce higher cost of farm products, meaning that the market price rises, becoming uncompetitive when compared to the prices of industrial products. Consequently, lower revenues can hinder the farm growth expected in the framework of the EU Green Deal. Since zoonosis control is a key element in aligning EU policies aimed at achieving the EU Green Deal goal of “ZERO environmental impact” by 2050, the authors suggest the inclusion of the parameter economic health in the OH approach, in order to individuate EU Member States (MSs) economically unable to conduct eradication programmes and to finance them. Economic health is here considered as a starting point of the new ethical and science-based One Health Financial Model that the authors suggest as an in-embryo model, in which specific rules should regulate public funds, private investments, and trading, which should exclusively concern public services and private enterprises complying with most of the OH parameters. In this way, economic losses due to collateral negative effects deriving from human activities can be progressively decreased, and the entire planet will benefit from the process. Despite the considerable efforts being carried out in the context of the OH approach, war causes tragic and devastating effects on the physical and mental health of human beings, on their lives, on pandemic and zoonotic threats, on animals, on plants and, last but not least, on the environment. War is incompatible with OH. Enormous efforts for peace are therefore urgently needed

Drosophila dyskerin is required for somatic stem cell homeostasis

Drosophila represents an excellent model to dissect the roles played by the evolutionary conserved family of eukaryotic dyskerins. These multifunctional proteins are involved in the formation of H/ ACA snoRNP and telomerase complexes, both involved in essential cellular tasks. Since fly telomere integrity is guaranteed by a different mechanism, we used this organism to investigate the specific role played by dyskerin in somatic stem cell maintenance. To this aim, we focussed on Drosophila midgut, a hierarchically organized and well characterized model for stemness analysis. Surprisingly, the ubiquitous loss of the protein uniquely affects the formation of the larval stem cell niches, without altering other midgut cell types. The number of adult midgut precursor stem cells is dramatically reduced, and this effect is not caused by premature differentiation and is cell-autonomous. Moreover, a few dispersed precursors found in the depleted midguts can maintain stem identity and the ability to divide asymmetrically, nor show cell-growth defects or undergo apoptosis. Instead, their loss is mainly specifically dependent on defective amplification. These studies establish a strict link between dyskerin and somatic stem cell maintenance in a telomerase-lacking organism, indicating that loss of stemness can be regarded as a conserved, telomerase-independent effect of dyskerin dysfunction

Malpractice and patient safety descriptors: an innovative grid to evaluate the quality of clinical records

Introduction: The medical record contains all the health information related to the patient’s clinical condition and its evolution during hospitalization. It was defined by the Italian Ministry of Health in 1992 as "The information tool designed to record all relevant demographic and clinical information about a patient during a single episode of hospitalization". The documents and information in a Medical Record must meet the following criteria: traceability, clarity, accuracy, authenticity, pertinence and completeness. The objectives of our study was to develop a tool capable of assessing the quality of the clinical record and pointed the critical point at the Organizational, Technical - Professional, Managerial level. Methods: To evaluate the quality of the medical documentation, we created an assessment grid composed of 4 sections with a total of 92 criteria. This grid was tested on 200 medical records that were randomly selected from 25 (18 medical and 7 surgical) wards of a teaching hospital in Rome. Results: The grid contains 4 sections. The first part regards administrative and clinical data; the second assesses the quality of hospital stay and surgical/invasive procedures; the third part is concerned with the discharge of the patient and the fourth aims to identify the presence of advisory reports given to the patient. This grid has been validated to verify internal consistency with Cronbach's Alpha = 0,743. Conclusions: Medical records were analyzed using a validated tool with grids to identify critical issues in care activities. Weaknesses in the system were identified in order to improve planning. The sample testing also in terms of ‘self-assessment' represents a tool to introduce activities to improve safety and quality of care, greatly reducing the costs of litigation

The Tumor Suppressor DAB2IP Is Regulated by Cell Contact and Contributes to YAP/TAZ Inhibition in Confluent Cells

External and internal mechanical forces modulate cell morphology, movement, proliferation and metabolism, and represent crucial inputs for tissue homeostasis. The transcriptional regulators YAP and TAZ are important effectors of mechanical signaling and are frequently activated in solid tumors, correlating with metastasis, chemoresistance, and shorter patient survival. YAP/TAZ activity is controlled by various pathways that sense cell shape, polarity, contacts, and mechanical tension. In tumors, aberrant YAP/TAZ activation may result from cancer-related alterations of such regulatory networks. The tumor suppressor DAB2IP is a Ras-GAP and scaffold protein that negatively modulates multiple oncogenic pathways and is frequently downregulated or inactivated in solid tumors. Here, we provide evidence that DAB2IP expression is sustained by cell confluency. We also find that DAB2IP depletion in confluent cells alters their morphology, reducing cell packing while increasing cell stiffness. Finally, we find that DAB2IP depletion in confluent cells favors YAP/TAZ nuclear localization and transcriptional activity, while its ectopic expression in subconfluent cells increases YAP/TAZ retention in the cytoplasm. Together, these data suggest that DAB2IP may function as a sensor of cell interactions, contributing to dampening cellular responses to oncogenic inputs in confluent cells and that DAB2IP loss-of-function would facilitate YAP/TAZ activation in intact epithelia, accelerating oncogenic transformation

Exercise with Energy Restriction as a Means of Losing Body Mass while Preserving Muscle Quality and Ameliorating Co-morbidities: Towards a Therapy for Obesity?

Exercise with Energy Restriction as a Means of Losing Body Mass while Preserving Muscle Quality and Ameliorating Co-morbidities: Towards a Therapy for Obesity? Antonia Giacco1*, Elena Silvestri1*, Rosalba Senese2, Federica Cioffi1, Arianna Cuomo2, Assunta Lombardi3, Maria Moreno1, Antonia Lanni2 and Pieter de Lange()2 1Dipartimento di Science e Tecnologie, Università degli Studi del Sannio, Benevento, Italy 2Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università degli Studi della Campania "Luigi Vanvitelli," Caserta, Italy 3Dipartimento di Biologia, Università degli Studi di Napoli "Federico II," Napoli, Italy © The Authors Abstract Obesity and related co-morbidities are a major public health threat worldwide, and efforts to counteract obesity by means of physiological interventions are currently being explored and applied. Here we present an overview of the literature on the effect of dietary/exercise-based programs on loss of different components of body mass. We also discuss gain or lack of loss of lean mass in view of muscle quality maintenance, which is an important aspect to consider when employing weight-loss strategies to tackle obesity. By comparing results obtained in participants with mild to severe obesity with those obtained in lean participants, we highlight variations in the success of these interventions. Furthermore, we briefly address the observation that although certain interventions may not always affect body composition they can nevertheless ameliorate co-morbidities (insulin resistance, non-alcoholic fatty liver disease). Based on what is currently known, in this narrative review we include data from human and animal studies related to the process of unravelling the mechanisms underlying conservation of functional muscle mass

Significant impact of pneumococcal conjugate vaccination on pediatric parapneumonic effusion: Italy 2006-2018

Abstract Etiology and serotyping of parapneumonic effusion (PPE) and the impact of vaccination was evaluated over a 12-year period, before and after the PCV13 introduction (2011) for Italian children From 0 to 16 years of age. Five hundred and two children were evaluated; 226 blood and 356 pleural fluid samples were obtained and tested using Realtime-PCR and culture. In the pre-PCV13 era S. pneumoniae was the most frequent pathogen identified (64/90; 71.1%) with a large predominance of serotypes 1 (42.4%), 3 (23.7%), 7F (5.1%) and 19A (11.9%). The impact of vaccination, calculated on children 0–8 years of age, demonstrated a significant reduction of PPE: with an incidence rate of 2.82 (95%CL 2.32–3.41) in the pre-PCV13 era and an age-standardized rate (ASR) of 0.66 (95% CL 0.37–1.99) in the post-PCV13 era, p  In conclusion, our findings indicate that routine immunization with PCV13 has significantly reduced the burden of childhood PPE in vaccinated children, without increasing PPE due to other bacteria and without serotype shift. Moreover, the impact of PCV13 may be underestimated due to the increase in pneumococcal surveillance in Italy. Data has also shown that Real-time PCR is an essential tool to better define the etiology of PPE and to monitor vaccination plans. Longer studies will be necessary to evaluate the role of herd protection in PPE prevention

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Simple Summary This clinical investigation reports the results of a prospective, multicenter phase II trial designed to evaluate the activity and safety of combining non-pegylated liposomal doxorubicin (NPLD) with ifosfamide as a first-line treatment for advanced/metastatic STS. The study results demonstrate a remarkable overall response rate (ORR) alongside a satisfactory disease control rate (DCR) while maintaining acceptable levels of toxicity. The addition of NPLD to ifosfamide, showing high activity and a low toxicity profile, makes this drug combination a useful option for patients with advanced/metastatic STS. These findings provide a promising basis for further comprehensive research into the clinical application of this drug combination in this disease setting.Abstract Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity