Proteomic Modulation in TGF-β-Treated Cholangiocytes Induced by Curcumin Nanoparticles

Curcumin is a natural polyphenol that exhibits a variety of beneficial effects on health, including anti-inflammatory, antioxidant, and hepato-protective properties. Due to its poor water solubility and membrane permeability, in the present study, we prepared and characterized a water-stable, freely dispersible nanoformulation of curcumin. Although the potential of curcumin nanoformulations in the hepatic field has been studied, there are no investigations on their effect in fibrotic pathological conditions involving cholangiocytes. Exploiting an in vitro model of transforming growth factor-  (TGF- )-stimulated cholangiocytes, we applied the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS)-based quantitative proteomic approaches to study the proteome modulation induced by curcumin nanoformulation. Our results confirmed the well-documented anti-inflammatory properties of this nutraceutic, highlighting the induction of programmed cell death as a mechanism to counteract the cellular damages induced by TGF- . Moreover, curcumin nanoformulation positively influenced the expression of several proteins involved in TGF- -mediated fibrosis. Given the crucial importance of deregulated cholangiocyte functions during cholangiopathies, our results provide the basis for a better understanding of the mechanisms associated with this pathology and could represent a rationale for the development of more targeted therapies

Need for psychological support and disability management programs during and after the COVID-19 pandemic in Italy: Preliminary findings from a hospital-based occupational health surveillance program

Introduction: Since the beginning of COVID-19 pandemic, healthcare workers (HCWs) have undoubtedly experienced overwhelming levels of strain associated with social and occupational stressors. This study aimed to investigate the potential psychological effects experienced by hospital workers and HCWs and their associated demographical and occupational characteristics during the COVID-19 pandemic. Methods: A cross-sectional study was carried out in a public hospital in Rome, Italy, from June 2020 to July 2021. 635 hospital workers (HCWs, administrative and technicians) were enrolled in the study. The “Psychological Injury Risk Indicator” questionnaire was used. Statistical analyses have been made using Student’s T test for categorical binomial variables and analysis of variance for multi-categorical variables. Logistic regression analysis was then performed. Results: 30.6% of the sample was at risk for general psychological impairment; reduced energy recovery was found in 48.0% and sleep problems in 44.7% of them. Female workers reported a two-fold risk for potential psychological impairment compared to male colleagues. Nurses presented a three-fold risk while physicians a two-fold risk for the overall score. Additionally, physicians had a four-fold risk to develop a lack of energy recovery and a three-fold risk for chronic fatigue. Technicians showed a significant double risk for sleep problems and chronic fatigue as well as a three-fold risk for reduced energy recovery. Administrative personnel reported a tendency on sleep problems. Interestingly, agile working was a two-fold protecting factor. No-night shifters have a half risk for reporting problems in energy recovery. Discussion and Conclusion: The measure of agile working is effective to mitigate the impacts of COVID-19 on mental health by protecting and promoting the psychological wellbeing of HCWs during and after the outbreak

Lipid biomarkers in statin users with coronary artery disease annotated by coronary computed tomography angiography

Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.Cardiolog

Effectiveness of psychological support to healthcare workers by the occupational health service: a pilot experience

Work-related stress is a significant risk for healthcare workers (HCWs). This study aims aevaluating the effectiveness of an individual psychological support programme for hospital workersIn all, 35 workers participated (n). A control group of 245 workers (7n) was set. Occupationadistress was measured by the General Health Questionnaire, (GHQ-12), the quality of life by the Short Form-36 health survey, (SF-36), and sickness absence was recorded. Costs and benefits of the service were evaluated and the return on investment (ROI) was calculated. The level of distress was significantly reduced in the treated group at the end of the follow-up (p < 0.001). Quality of life had significantly improved (p < 0.003). A 60% reduction of sickness absence days (SADs) following the intervention was recorded. After the treatment, absenteeism in cases was significantly lower than in controls (p < 0.02). The individual improvement of mental health and quality of life was significantly correlated with the number of meetings with the psychologist (p < 0.01 and p < 0.03, respectively)The recovery of direct costs due to reduced sick leave absence was significantly higher than the costs of the programme; ROI was 2.73. The results must be examined with caution, given the very limited number of workers treated; this first study, however, encouraged us to continue the experience

Characterization of the Escherichia coli pyridoxal 5'-phosphate homeostasis protein (YggS): Role of lysine residues in PLP binding and protein stability

The pyridoxal 5'-phosphate (PLP) homeostasis protein (PLPHP) is a ubiquitous member of the COG0325 family with apparently no catalytic activity. Although the actual cellular role of this protein is unknown, it has been observed that mutations of the PLPHP encoding gene affect the activity of PLP-dependent enzymes, B6 vitamers and amino acid levels. Here we report a detailed characterization of the Escherichia coli ortholog of PLPHP (YggS) with respect to its PLP binding and transfer properties, stability, and structure. YggS binds PLP very tightly and is able to slowly transfer it to a model PLP-dependent enzyme, serine hydroxymethyltransferase. PLP binding to YggS elicits a conformational/flexibility change in the protein structure that is detectable in solution but not in crystals. We serendipitously discovered that the K36A variant of YggS, affecting the lysine residue that binds PLP at the active site, is able to bind PLP covalently. This observation led us to recognize that a number of lysine residues, located at the entrance of the active site, can replace Lys36 in its PLP binding role. These lysines form a cluster of charged residues that affect protein stability and conformation, playing an important role in PLP binding and possibly in YggS function

Diagnostic and therapeutic care pathway for fibromyalgia

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals

Fibromyalgia position paper

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients