Epigenetic Changes Predisposing to Type 2 Diabetes in Intrauterine Growth Retardation

Epidemiologic studies have demonstrated an association between intrauterine growth retardation and a greater risk of chronic disease, including coronary heart disease, hypertension, stroke, and type 2 diabetes in adulthood. An adverse intrauterine environment may affect both growth and development of the organism, permanently programming endocrine and metabolic functions. One of the mechanisms of programming is the epigenetic modification of gene promoters involved in the control of key metabolic pathways. The aim of this review is to provide an overview of the experimental evidence showing the effects of early exposure to suboptimal environment on epigenome. The knowledge of the epigenetic markers of programming may allow the identification of susceptible individuals and the design of targeted prevention strategies

Molecular Analysis of Prothrombotic Gene Variants in Venous Thrombosis: A Potential Role for Sex and Thrombotic Localization

Background: Requests to test for thrombophilia in the clinical context are often not evidence-based. Aim: To define the role of a series of prothrombotic gene variants in a large population of patients with different venous thromboembolic diseases. Methods: We studied Factor V Leiden (FVL), FVR2, FII G20210A, Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, beta-fibrinogen -455 G>A, FXIII V34L, and HPA-1 L33P variants and PAI-1 4G/5G alleles in 343 male and female patients with deep vein thrombosis (DVT), 164 with pulmonary embolism (PE), 126 with superficial vein thrombosis (SVT), 118 with portal vein thrombosis (PVT), 75 with cerebral vein thrombosis (CVT) and 119 with retinal vein thrombosis (RVT), and compared them with the corresponding variants and alleles in 430 subjects from the general population. Results: About 40% of patients with DVT, PE and SVT had at least one prothrombotic gene variant, such as FVL, FVR2 and FII G20210A, and a statistically significant association with the event was found in males with a history of PE. In patients with a history of PVT or CVT, the FII G20210A variant was more frequent, particularly in females. In contrast, a poor association was found between RVT and prothrombotic risk factors, confirming that local vascular factors have a key role in this thrombotic event. Conclusions: Only FVL, FVR2 and FII G20210A are related to vein thrombotic disease. Other gene variants, often requested for testing in the clinical context, do not differ significantly between cases and controls. Evidence of a sex difference for some variants, once confirmed in larger populations, may help to promote sex-specific prevention of such diseases

Functioning issues in inpatients affected by COVID-19-related moderate pulmonary impairment: a real-practice observational study

Objective To investigate the correlations between clinical, functional, and radiological outcomes in inpatients with coronavirus disease 2019 (COVID-19). Methods In this observational study, we recruited inpatients affected by moderate COVID-19 disease. The clinical evaluation comprised the Cumulative Illness Rating Scale (CIRS), numerical rating scale (NRS), modified Rankin scale (mRS), and the modified Borg dyspnea scale (mBDS). Respiratory involvement was assessed with computed tomography (CT) and graded with a CT-severity score (CT-SS). We retrospectively assessed functioning using the International Classification of Functioning, Disability and Health (ICF) codes of the Clinical Functioning Information Tool (ClinFIT) COVID-19 in the acute phase. Correlation analysis was performed 1) between clinical, instrumental, and functional parameters and 2) between ICF categories. Results The data showed statistically significant moderate correlations between CT-SS and the following categories: b152 “emotional functions” and b440 “respiratory functions”. Conclusion This is the first study to use the ICF framework in people with a moderate form of COVID-19 in the acute phase. Considering the correlations between some ICF categories and radiological findings, our results support the use of the ClinFIT COVID-19 for a comprehensive assessment of COVID-19 patients

Atypical Fibroxanthoma-Like Amelanotic Melanoma: A Diagnostic Challenge

Atypical fibroxanthoma-like amelanotic melanoma is a very rare variant of melanoma that can, if not correctly recognized and framed, lead to diagnostic errors that can potentially cause problems of extreme relevance to patients. Correct knowledge of this entity and the execution of adequate immunohistochemical investigations are the basic conditions for the correct management of this lesion. We report on a case of atypical fibroxanthoma-like amelanotic melanoma, which clinically simulated a fibrohistiocytic lesion, and which created differential diagnostic problems, and finally, we conduct a short review of the literature

A failure mode and effect analysis (FMEA)-based approach for risk assessment of scientific processes in non-regulated research laboratories

AbstractNowadays, Quality Management tools such as failure mode and effect analysis (FMEA) are widely used throughout the aeronautical, automotive, software, food services, health care and many other industries to sustain and improve quality and safety. The increasing complexity of scientific research makes it more difficult to maintain all activities under control, in order to guarantee validity and reproducibility of results. Even in non-regulated research, scientists need to be supported with management tools that maximize study performance and outcomes, while facilitating the research process. Frequently, steps that involve human intervention are the weak links in the process. Risk analysis therefore gives considerable benefit to analytical validation, assessing and avoiding failures due to human error, potential imprecision in applying protocols, uncertainty in equipment function and imperfect control of materials. This paper describes in detail how FMEA methodology can be applied as a performance improvement tool in the field of non-regulated research, specifically on a basic Life Sciences research process. We chose as "pilot process" the selection of oligonucleotide aptamers for therapeutic purposes, as an example of a complex and multi-step process, suitable for technology transfer. We applied FMEA methodology, seeking every opportunity for error and its impact on process output, and then, a set of improvement actions was generated covering most aspects of laboratory practice, such as equipment management and staff training. We also propose a useful tool supporting the risk assessment of research processes and its outputs and that we named "FMEA strip worksheet." These tools can help scientists working in non-regulated research to approach Quality Management and to perform risk evaluation of key scientific procedures and processes with the final aim to increase and better control efficiency and efficacy of their research

Chapter Il Piccolo Masaccio e le Terre Nuove. Creativity and Computer Graphics for Museum Edutainment

Since its opening, the Museum of the New Towns, housed in the Palazzo di Arnolfo in San Giovanni Valdarno, has dedicated a particular attention to the relationship with its audiences. In this context, the video “Il piccolo Masaccio e le Terre Nuove” has the purpose of bringing children and young people, in particular, closer to the museum main themes. The video presents a series of very different techniques, such as live shots, taken also by drone, Computer Graphics, 2D drawings executed with a tablet, drawings sketched with traditional techniques, such as India ink and watercolours, and digital videos taken from Google Earth

The Brief Strategic Treatment of Cardiophobia: A Clinical Case Study

AbstractMany individuals presenting to medical settings with heart-related symptoms for which no medical explanation is found might suffer from cardiophobia, but this condition is still poorly identified and addressed. This article presents a case of cardiophobia treated in an outpatient cardiac rehabilitation unit and, for the first time, describes the application of brief strategic therapy for the treatment of this condition. In the case reported, the first therapeutic encounter and the key elements of the strategic approach are described in detail with the aim to explain how brief strategic therapy works and how it can be used to identify and address cardiophobia-related behaviors. A 64-year-old male presented to cardiac rehabilitation reporting intense anxiety-provoking heart palpitations, and believing he was at risk of dying from a heart attack. After 3 sessions, an overall improvement in heart-related bodily sensations followed a decrease in the patient's continuous checking of his heartbeat and seeking reassurance—factors that were largely responsible for the persistence of the problem. Moreover, quantitative evaluation showed increased scores of mood state at the end of treatment. This improvement persisted at the 18-month follow-up. This case is an interesting example of how brief strategic therapy can contribute to the development of a new conceptual model for the diagnosis and treatment of cardiophobia. Still, more systematic research in the field is needed to prove the efficacy and effectiveness of this therapeutic approach on symptoms of heart-focused anxiety

MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines

MicroRNA (miR)-199b-5p has been shown to regulate Hes-1, a downstream effector of the canonical Notch and noncanonical SHH pathways, whereby it impairs medulloblastoma (MB) cancer stem cells (CSCs) through a decrease in the CD133+/CD15+ cell population. Here, we have developed stable nucleic acid lipid particles (SNALPs) that encapsulate miR-199b-5p. The efficacy of the miR- 199b-5p delivery by these SNALPs is demonstrated by significant impairment of Hes-1 levels and CSC markers in a range of different tumorigenic cell lines: colon (HT- 29, CaCo-2, and SW480), breast (MDA-MB231T and MCF-7), prostate (PC-3), glioblastoma (U-87), and MB(Daoy, ONS-76, and UW-228). After treatment with SNALP miR-199b-5p, there is also impairment of cell pro- liferation and no signs of apoptosis, as measured by cas- pases 3/7 activity and annexin V fluorescence cell sorter analyses. These data strengthen the importance of such carriers for miRNA delivery, which show no cytotoxic effects and provide optimal uptake into cells. Thus, efficient target downregulation in different tumorigenic cell lines will be the basis for future preclinical studies

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients