Creation of a Forensic Pathology Biobank in Switzerland: which issues and research opportunities?

A biobank is a collection of biological material associated with health database. The field of biobanking has significantly developed over the past 30 years. Research based on biobank material gives access to data of a large number of people and can often significantly accelerate the understanding of disease and improve the quality of care. In the University Center of Legal Medicine Lausanne-Geneva, samples collected during autopsies are used for forensic investigations. The legal and ethical framework to use these samples for research is often complex and confused, which is unfortunate given the potential of these biospecimens. Indeed, forensic samples are valuable for research because they originate in part from young (including pediatrics cases) and healthy people who are poorly represented in worldwide institutional biobanks. In this context at the beginning of the year 2019, the Forensic Pathology Biobank was created. Creation of a forensic pathology biobank is the best way to standardize local conservation practices and improve personal data management, thus providing a very valuable biological material for scientific projects. Its development gives rise to many questions about technical standards, ethical and legal issues but also many research opportunities.

Nitrous oxide occupational exposure in conscious sedation procedures in dental ambulatories: a pilot retrospective observational study in an Italian pediatric hospital.

BACKGROUND: Nitrous oxide has a proven clinical efficacy in conscious sedation. At certain environmental concentrations it may pose a health risk to chronically exposed healthcare workers. The present pilot study aims at evaluating the exposure to nitrous oxide of dental ambulatory personnel of a pediatric hospital. METHODS: A descriptive study design was conducted in two phases: a bibliographic analysis on the environmental safety policies and a gas concentration analysis in the dental ambulatories of a pediatric hospital, detected every 6 months from December 2013 to February 2017 according to law provisions. The surveys were carried out using for gas analysis a photoacoustic spectrometer Innova-B&K "Multi-gas monitor model 1312" and Innova-B&K "Multi-sampler model 1309". The biological analysis and monitoring have been carried out on staff urine. RESULTS: The analyses were performed during 11 dental outpatient sessions on pediatric patients. All the patients were submitted to the same dental procedures, conservative care and dental extractions. The pediatric patients were 47 (23 males, 24 females; age range 3-17 years; mean age 6,63, SD ± 2,69) for a mean of 4,27 (SD ± 1,49) per session., The mean environmental concentration of nitrous oxide during the sessions was 24.7 ppm (SD ±16,16). A correlation was found between urinary nitrous oxide concentration of dentists (Pearson's correlation 0.786; p = 0.007) and dental assistants urines (Pearson's correlation 0.918; p < 0.001) and environmental concentrations of nitrous oxide. Weak negative correlations were found between age and sex of patients and environmental concentrations of nitrous oxide. The mean values of the biological monitoring data referring to all the outpatient sessions are lower than the reference values foreseen in accordance to the regulations in force on nitrous oxide concentration. CONCLUSIONS: The mean environmental concentration values recorded in our study are below the limit of 50 ppm considered as a reference point, a value lower than those reported in other similar surveys. The results of the present study provide a contribution to the need to implement technical standards, criteria and system requirements for the dental ambulatories, to date not yet completely defined, and cannot be assimilated to the ones established for the surgical rooms.

Frailty screening and assessment tools: a review of characteristics and use in Public Health.

INTRODUCTION: Frailty screening and assessment are a fundamental issue in Public Health in order to plan prevention programs and services. METHODOLOGY: By a narrative review of the literature employing the International Narrative Systematic Assessment tool, the authors aims to develop an updated framework for the main procedures and measurement tools to assess frailty in older adults, paying attention to the use in the primary care setting. RESULTS: The study selected 10 reviews published between January 2010 and December 2016 that define some characteristics of the main tools used to measure the frailty. Within the selected reviews only one of the described tools met all the criteria (multidimensionality, quick and easy administration, accurate risk prediction of negative outcomes and high sensitivity and specificity) necessary for a screening tool. CONCLUSION: Accurate risk prediction of negative outcomes could be the appropriate and sufficient criteria to assess a tool aimed to detect frailty in the community-dwelling elderly population. A two-step process (a first short questionnaire to detect frailty and a second longer questionnaire to define the care demand at individual level) could represent the appropriate pathway for planning care services at community level.

The European Innovation Partnership on Active and Healthy Ageing Synergies: Protocol for a Prospective Observational Study to Measure the Impact of a Community-Based Program on Prevention and Mitigation of Frailty (ICP - PMF) in Community-Dwelling Older Adults.

Aim of this paper is to describe the protocol of the study "Impact of a Community-based Program on Prevention and Mitigation of Frailty in community-dwelling older adults" developed in the framework of the European Innovation Partnership on Active and Healthy Ageing. This proposal has been developed by the Partnership Action groups on frailty, fall prevention and polypharmacy in older. The proposal wants to assess the impact of community-based programs aimed to counteract three main outcomes related to frailty: hospitalization, institutionalization and death. Bringing together researchers from seven European countries, the proposal aims to achieve the critical mass and the geographical extension enough to provide information useful to all older European citizens. An observational study will be carried out to calculate the incidence of the different outcomes in relation to the various interventions that will be assessed; results will be compared with data coming from already established national, regional and local dataset using the observed/expected approach. The sample will be made up by at least 2000 citizens for each outcome. All the citizens will be assessed at the baseline with two multidimensional questionnaires: the RISC questionnaire and the Short Functional Geriatric Evaluation questionnaire. The outcomes will be assessed every six-twelve months.

Trend and determinants of acute inpatient care for the elderly in Italy from 2001 to 2011.

BACKGROUND: The population over 64 years of age is the main user of acute hospital care services. The elderly admission rates represent a marker for the appropriateness of the model of care. The aim of this study was to assess trends and determinants of acute in-patient care among the elderly in Italy between 2001 and 2011. STUDY DESIGN: Retrospective analysis of data included in the Italian Hospital Discharge Form Database. METHODS: Data from the Italian Hospital Discharge Form Database, Italian Ministry of Health, for the years 2001, 2006 and 2011 were analyzed for individuals over 64 years of age. Inpatient admission (> 1 day) rates across Italian Regions were calculated and compared with demographic variables and out-of-hospital care indicators. Univariate and multivariate analysis were used to determine independent relationship among variables. RESULTS: From 2001 to 2011 the elderly hospital admission rate decreased from 302.1/1,000 in 2001, to 222.4 in 2011, accounting for an overall decrease of about 28%. The decline in admission rates was less pronounced among individuals > 74 y (26.4%) than among those 65-74 y (32.1%). Hospitalization rates decreased in all Italian administrative regions between 2001 and 2011, even if the hospitalization rates in 2011 were still very different through the different Italian regions, ranging from 180.3/1,000 in Piedmont to 278.1/1,000 in Molise for people > 64 y. The multivariate linear regression was statistically significant in explaining the variations in hospitalization rates among the different Italian administrative regions (F: 3.637; p = 0.024; adjusted R2 = 0.57) and pointed to the role played by the proportion of the elderly (as percentage of the total population, p=0.043) and the rate of variation of acute care beds from 2004 to 2011 (p=0.001). Variables related to community-based care did not show any association with the hospital admissions rate among the elderly. CONCLUSIONS: The trend toward decline in elderly inpatient admissions is still present in 2011 as it was in 2001. Determinants of elderly hospital care in Italy are related to the increased number of elderly individuals and the reduction of hospital beds. Out-of-hospital care does not correlate with the variation of in-patient care so the overall care appropriateness could be negatively affected.

Testing the accuracy ratio of the Spatio-Temporal Epidemiological Modeler (STEM) through Ebola haemorrhagic fever outbreaks.

Mathematical modelling is an important tool for understanding the dynamics of the spread of infectious diseases, which could be the result of a natural outbreak or of the intentional release of pathogenic biological agents. Decision makers and policymakers responsible for strategies to contain disease, prevent epidemics and fight possible bioterrorism attacks, need accurate computational tools, based on mathematical modelling, for preventing or even managing these complex situations. In this article, we tested the validity, and demonstrate the reliability, of an open-source software, the Spatio-Temporal Epidemiological Modeler (STEM), designed to help scientists and public health officials to evaluate and create models of emerging infectious diseases, analysing three real cases of Ebola haemorrhagic fever (EHF) outbreaks: Uganda (2000), Gabon (2001) and Guinea (2014). We discuss the cases analysed through the simulation results obtained with STEM in order to demonstrate the capability of this software in helping decision makers plan interventions in case of biological emergencies.

Unequal access, low vaccination coverage, growth retardation rates among immigrants children in Italy exacerbated in Roma immigrants.

AIM: Currently children of immigrants are the fastest growing segment of the Italian population under the age of 18. The present study reports the challenges to health services access, the vaccination coverage, the health and nutritional status of a sample of 1310 children of immigrants attended from February 2004 to May 2012 the health center "Medicina Solidale" of the "Policlinico Tor Vergata" in the suburban area of the VIII Municipality of Rome. METHODS: The data were collected using clinical archives of the health center. We analyzed the socio-demographic conditions, health problems and nutritional status on admission to the health center. The anthropometric evaluation was carried out according to international standards of child growth WHO 2006 and the statistical analysis was performed using SPSS version 19, and including risk estimation, Mantel Haentzel statistics and t-test. RESULTS: Sixty-six percent of the children were born in Italy, 62% had never had regular health care and 3.4% of children older than six months had never received any of the immunizations. It has been estimated that being Roma the risk of not been vaccinated is equal to OR=5.4 (IC95%: 2.8-10.1). Seventy-seven percent of unvaccinated children had at least one illiterate parent. This condition was strongly associated with non-immunization (OR=15:36 [IC95%: 6.4-36.4]). Growth retardation was common in Roma children as compared to other ethnicities. CONCLUSION: Significant public health efforts are needed to improve access to health services for immigrant populations and to solve relevant inequalities.

[Inconsistency between voltage of the electrocardiogram and the left ventricular wall thickness. diagnostic key in cardiac amyloidosis]. / Discordancia entre el voltaje del electrocardiograma y el grosor parietal del ventículo izquierdo. clave diagnóstica en amiloidosis cardíaca.

Restrictive cardiomyopathy is the least common form of cardiomyopathy, and the disease that most often cause it, is the system amyloidosis. We present a 62-year-old with a history of heart failure, which in its assessment highlights the discrepancy between the low voltage ventricular complexes in the electrocardiogram and the severity of left ventricular wall thickness on echocardiography. This discrepancy was the source of suspicion and subsequent confirmation of systemic amyloidosis with cardiac involvement.

La miocardiopatía restrictiva es la forma menos frecuente de cardiomiopatía, y la enfermedad que con mayor frecuencia la origina, es la amiloidosis sistema. Presentamos un paciente de 62 años, con antecedentes de insuficiencia cardiaca, que en su evaluación, destaca la discordancia entre el escaso voltaje de los complejos ventriculares en el electrocardiograma y la severidad del grosor parietal del ventrículo izquierdo en el ecocardiograma, siendo dicha discordancia, la fuente de sospecha y posterior confirmación de amiloidosis sistémica con compromiso cardiaco.

Discordancia entre el voltaje del electrocardiograma y el grosor parietal del ventículo izquierdo. clave diagnóstica en amiloidosis cardíaca / [Inconsistency between voltage of the electrocardiogram and the left ventricular wall thickness. diagnostic key in cardiac amyloidosis].

Restrictive cardiomyopathy is the least common form of cardiomyopathy, and the disease that most often cause it, is the system amyloidosis. We present a 62-year-old with a history of heart failure, which in its assessment highlights the discrepancy between the low voltage ventricular complexes in the electrocardiogram and the severity of left ventricular wall thickness on echocardiography. This discrepancy was the source of suspicion and subsequent confirmation of systemic amyloidosis with cardiac involvement.

Discordancia entre el voltaje del electrocardiograma y el grosor parietal del ventículo izquierdo. clave diagnóstica en amiloidosis cardíaca. / [Inconsistency between voltage of the electrocardiogram and the left ventricular wall thickness. diagnostic key in cardiac amyloidosis].

Restrictive cardiomyopathy is the least common form of cardiomyopathy, and the disease that most often cause it, is the system amyloidosis. We present a 62-year-old with a history of heart failure, which in its assessment highlights the discrepancy between the low voltage ventricular complexes in the electrocardiogram and the severity of left ventricular wall thickness on echocardiography. This discrepancy was the source of suspicion and subsequent confirmation of systemic amyloidosis with cardiac involvement.

Synthesis, characterization and biological evaluation of ureidofibrate-like derivatives endowed with peroxisome proliferator-activated receptor activity.

A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARγ-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARγ target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARα target genes indicating that their in vivo effects stemmed from an activation of both PPARα and γ. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated.

[Acute hospital care for the elderly in Italy: comparison between 2001 and 2006]. / L'assistenza ospedaliera per la popolazione anziana in Italia: un confronto tra 2001 e 2006.

The continous health expenditure increase in developed countries is often related with the acute hospital care of the elderly. To monitor the characteristics of elderly acute hospital care included the expenditure trend is crucial in order to identify the appropriateness of this care. The aim of this study is to describe quality and quantity of in-hospital care use of elderly population in Italy in 2006 and to compare the results with the same information gathered for 1996 and 2001. All the 2006 acute hospital admission longer than one day of the patients older than 64 years sourced from the Register of Discharge Form of the Italian Ministry of Health have been analyzed. A list of the 30 more frequent diagnoses has been compiled and compared with the same list compiled for 2001. On the basis of the National Fee for each Disease Related Group an analysis of the hospital expenditure has been carried out. The correlation between DRGs National Fees and frequency of the diagnosis in the discharge form has been based on the 80 diagnosis that has been recorded for more than 10.000 discharge forms in 2006. A relevant increase of acute hospital admission for respiratory, cardiovascular and urinary pathologies among the elderly has been observed. Moreover the number of hospital admissions for major joints and implant of lower limbs is doubled from 1996. The total health expenditure for the elderly acute care longer than one day is increased of 6.3% and a positive correlation between higher DRGs fees and higher frequency of diagnosis has been observed (Pearson correlation value = 0.478; p<0.001 - cubic regression R-square value = 0.301; p<0.001). The hospital acute care use of the elderly patients seems to be more related to emergency care than in the past, while a decrease of DRGs related to chronic diseases and generic diagnosis has been observed. The more frequent cause of in-hospital admission seems to be related also to a higher DRGs fee. As already observed in the past years, a trend towards the use of more expensive DRGs could be detected.

Expression of sterol 27-hydroxylase in glial cells and its regulation by liver X receptor signaling.

Cholesterol is required in the brain for synaptogenesis and its turnover is critical for cerebral functions. Several proteins involved in cholesterol handling and metabolism are transcriptionally regulated by the nuclear liver X receptor (LXR) alpha and beta. Sterol 27-hydroxylase (CYP27) is a ubiquitously expressed enzyme involved in cholesterol metabolism. Notably, its deficiency causes a disease characterized by progressive neurologic impairment. With the final goal to understand the pathophysiological role of CYP27A1 in the CNS, we studied the expression pattern of Cyp27a1 and other related genes in primary cultures of rat glia and neurons. Secondly, given the pivotal role of LXR in the regulation of cholesterol homeostasis, we investigated the effects of its activation on the expression of Cyp27a1.We found that primary astrocytes express different sterol hydroxylases and are able to uptake exogenous 27-hydroxycholesterol. We found that both microglia and astrocytes express preferentially Lxrbeta. However, despite this similarity, we observed cell-specific responsiveness of known and novel (including Cyp27a1) target genes to LXR activation. The increase of mRNA and protein levels in treated astrocytes is paralleled by transactivation of the proximal Cyp27a1 promoter in transfected astrocytes. We suggest that the astrocyte-restricted up-regulation of Cyp27a1 may be ascribable to differential expression of transcriptional co-activators. Given the role of astrocytes in maintaining brain homeostasis, we hypothesize that impairment of CYP27 activity in these cells may alter critical features of the astrocytes, from the handling and delivery of cholesterol to neurons to the release of signaling molecules.

Bile acids and their signaling pathways: eclectic regulators of diverse cellular functions.

The field of bile acids has witnessed an impulse in the last two decades. This has been the result of cloning the genes encoding enzymes of bile acid synthesis and their transporters. There is no doubt that the identification of Farnesoid X Receptor (FXR, NR1H4) as the bile acid receptor has contributed substantially to attract the interest of scientists in this area. When FXR was cloned by Forman et al. [1], farnesol metabolites were initially considered the physiological ligands. After identifying FXR and other nuclear receptors as bile acid sensors [2-4], it has become clear that bile acids are involved in the regulation of lipid and glucose metabolism and that these molecules are eclectic regulators of diverse cellular functions. In this review, we will summarize the current knowledge of the functions regulated by bile acids and how their physiological receptors mediate the signaling underlying numerous cellular responses.

LXR (liver X receptor) and HNF-4 (hepatocyte nuclear factor-4): key regulators in reverse cholesterol transport.

Cholesterol homoeostasis is the result of the fine tuning between intake and disposal of this molecule. High levels of cholesterol in the blood are detrimental as they may lead to excessive accumulation in vessel walls, a condition predisposing to the development of atherosclerotic lesions. Cholesterol is removed from the vessel wall and transported to the liver through a process called reverse cholesterol transport. Nuclear receptors are among the most important transcription factors regulating genes involved in different steps of reverse cholesterol transport. Here, we discuss the role of the nuclear receptors LXR (liver X receptor) and HNF-4alpha (hepatocyte nuclear factor-4alpha) in different steps of reverse cholesterol transport. LXR controls the transcription of crucial genes in cholesterol efflux from macrophages and its transport to the liver, such as ABCA1 (ATP binding cassette A1), CYP27A1 (sterol 27-hydroxylase), CLA-1 (scavenger receptor type B1) and apolipoprotein E. Some oxysterols present in oxidized low-density lipoproteins and proinflammatory cytokines modulate the activity of LXR by antagonizing the effect of activators of this receptor, thus contributing to cholesterol accumulation in macrophages. Bile acid synthesis, which represents the final step of reverse cholesterol transport, is transcriptionally regulated by several nuclear receptors at the level of the liver-specific cytochrome P450 cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme of this metabolic pathway. Bile acids returning to the liver through the enterohepatic circulation down-regulate CYP7A1 transcription via the bile acid sensors farnesoid X receptor and HNF-4alpha. Based on this evidence, these nuclear receptors are candidate targets of new drugs for the treatment and prevention of atherosclerotic disease.