Innovation and development after the earthquake in Emilia

The 2012 earthquake in Emilia-Romagna (Italy) has shaken up the collective understanding on the socioeconomic importance of a vast territory that generates almost 2% of Italian GDP. The area affected by the earthquake is characterized by the presence of important industrial and agricultural districts, and by good practices of local governance that are internationally renowned. Private and public buildings, factories, offices and retail shops, historical and cultural heritage sites have been severely damaged. Not only, but it set in motion transformations in the socio-economic system that might have unexpected consequences and that undermine the quick recovery of the local system: different agents, at different levels, taking individual and collective decisions, generate a cascade of changes that interact with its evolution path. Indeed, earthquakes pose challenges, but provide unprecedented opportunities: strategic decisions by economic and political agents, newly available financial resources, coordination or lack of coordination among main stakeholders, and so on. The following paper provides an overview of the first results of Energie Sisma Emilia research project: it aims at collecting and disseminating relevant knowledge and evidence in order to design policies. In particular, it identifies the agents propelling innovation processes, and analyses their strategies in ever-changing environment. The paper starts with a socio-economic analysis of the area struck by the earthquake, followed by the results of three of the focus groups conducted. Eventually, it illustrates a specific innovation: the introduction and implementation of the digital infrastructure “Mude”

Socio-demographic and clinical predictors of post-acute, mid-and long-term psychological sequelae of COVID-19: a two-year cross-sectional investigation on 1317 patients at the University Hospital of Verona

Background: The present paper focuses on socio-demographics, clinical variables, and the distance from the infection in predicting the long-term psycho-social consequences of COVID-19. Methods: Patients were screened with a cross-sectional design at the Psychological Service of the University Hospital of Verona (Italy) at 3, 6, 12, and 18 months after their SARS-CoV-2 infection. The assessment was part of the Horizon 2020-funded ORCHESTRA Project and included the Hospital Anxiety and Depression Scale (HADS), the Short Form Health Survey 36 (SF-36), the Impact of Event Scale-Revised (IES-R), and ad-hoc questions measuring pre-post COVID-19 changes on psycho-social dimensions (sleep quality, nutrition, level of autonomy, work, social relationships, emotional wellbeing). Results: Between June 2021 and June 2023, we evaluated 1317 patients (mean age 56.6 ± 14.8 years; 48% male): 35% at three months, 40% at 6, 20% at 12, and 5% at 18 months after the infection. Thirty-five percent were hospitalized due to COVID-19. Overall, 16% reported some form of clinically significant mental distress following the infection (HADS-TOT), with 13% and 6%, respectively, experiencing anxiety (HADS-Anxiety) and depressive symptoms (HADS-Depression). Four percent testified post-traumatic symptoms. The SF-36 scale revealed that 16% and 17% of subjects had physical or psychological deterioration in quality of life, respectively. The regression analyses showed that females experienced higher levels of anxiety and depression compared to males, along with worse mental and physical quality of life and pre-post infection changes in nearly all the investigated psycho-social dimensions. Younger people felt more anxiety and had a reduced mental quality of life than their older counterparts, who, in turn, had poorer scores in terms of autonomy and physical functioning. Hospitalized patients had lower levels of self-sufficiency, social relationships, and work than non-hospitalized people. The latter were more anxious and reported a lower physical quality of life. Finally, patients evaluated for the first time at 12- and 18 months showed a more significant impairment in mental and physical quality of life than those assessed at three months. Conclusions: Our data show that COVID-19 psychological sequelae tend to persist over time, still needing clinical attention and intervention planning, especially for females

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

Insolita causa di addome acuto in paziente adulto: l’ileo biliare

L’ileo biliare è una condizione morbosa rara descritta tra le complicanze della litiasi della colecisti. È causa dell’1-3% delle ostruzioni meccaniche del piccolo intestino. Interessa più frequentemente pazienti di età compresa tra 63 e 85 anni. La diagnosi pre-operatoria è generalmente posta con ritardo variabile da 1 a 10 giorni per l’assenza di una sintomatologia specifica. Caso clinico. Gli Autori riportano il caso di un uomo di 50 anni in cui è stata posta diagnosi di occlusione meccanica del piccolo intestino da voluminosa concrezione litiasica. L’occlusione ileale è stata dimostrata con la TC. Il paziente è stato sottoposto in urgenza ad intervento chirurgico, in un unico tempo, di enterolitotomia, colecistectomia e riparazione della fistola duodenale. Il decorso clinico è stato regolare e il paziente è stato dimesso in XIV giornata. Discussione. Nel nostro caso la diagnosi di ileo biliare è stata posta con un ritardo di 5 giorni. L’ecotomografia del fegato e delle vie biliari non è stata in grado di visualizzare la colecisti. La diagnosi è stata posta con la TC che si conferma gold standard diagnostico. Conclusioni. Lo stato clinico del paziente influenza la strategia chirurgica. Nel nostro paziente, considerato a basso rischio, è stato possibile l’intervento chirurgico in un unico tempo. La procedura in due tempi, enterolitotomia e successiva colecistectomia con riparazione della fistola, va riservata ai pazienti ad alto rischio

Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection.

Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD

A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level

<p>Abstract</p> <p>Background</p> <p>Serum creatinine (S_CR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in S_CRlevel is explicable by genetic factors.</p> <p>Methods</p> <p>We performed a meta-analysis of genome-wide association studies of S_CRundertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with S_CR(candidate loci) were replicated in two additional population-based samples ('replication cohorts').</p> <p>Results</p> <p>After the discovery meta-analysis, 29 loci were selected for replication. Association between S_CRlevel and polymorphisms in the collagen type XXII alpha 1 (<it>COL22A1</it>) gene, on chromosome 8, and in the synaptotagmin-1 (<it>SYT1</it>) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 × 10^-6and 1.7 × 10^-4, respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (<it>GABRR2</it>) gene and the ubiquitin-conjugating enzyme E2-J1 (<it>UBE2J1</it>) gene (replication p value = 3.6 × 10^-3). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (<it>UMOD</it>) gene and in the schroom family member 3 (<it>SCHROOM3</it>) gene were also replicated.</p> <p>Conclusions</p> <p>While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes <it>SYT1 </it>and <it>GABRR2 </it>corroborate previous findings that highlighted a possible role of the neurotransmitters GABA_Areceptors in the regulation of the glomerular basement membrane and a possible interaction between GABA_Areceptors and synaptotagmin-I at the podocyte level.</p

Comparison of glomerular filtration rate estimating formulas among Japanese adults without kidney disease

BackgroundPrevious studies have proposed different formulas of estimating glomerular filtration rate (eGFR) among clinical patients. The comprehensive comparison of eGFR formulas is not well established in a Japanese population. We compared eGFR values and chronic kidney disease (CKD) classification of nine different eGFR in a Japanese general population sample.MethodsWe analyzed 469 Japanese community-dwelling adults (184 men) without any self-reported kidney disease. GFR estimated using the 4- and 6-parameter Modification of Diet in Renal Disease (MDRD) formulas (MDRD4 and MDRD6); the CKD-EPI formulas based on creatinine with (CKD-EPI-2009) and without race coefficient (CKD-EPI-2021), on cystatin C (CKD-EPI-Cys), on both (CKD-EPI-CreCys); the Japanese creatinine-based formula (JPN-Cre), cystatin C-based formula (JPN-Cys), and modified CKD-EPI formula (JPN-CKD-EPI). CKD stages were defined by KDIGO guidelines (eGFR 2).ResultseGFRJPN-Cre (mean = 71.2; SD = 14.3) were much lower than eGFRCKD-EPI-2021 (mean = 94.2; SD = 12.7), while eGFRJPN-Cys (mean = 102.8; SD = 24.2) was comparable to the MDRD and CKD-EPI formulas. The difference between eGFRCKD-EPI-2021 and eGFRJPN-Cre showed a V-shaped distribution across eGFR levels, indicating complex errors between these formulas. We observed very low agreement in CKD classification between eGFRJPN-Cre and the eGFRCKD-EPI-2021 (kappa = 0.13; 95% confidence interval: 0.06, 0.23).ConclusionsJPN-Cre was substantially different from the CKD-EPI formula without race term (CKD-EPI-2021), which means that it is impossible to recalibrate those with a simple coefficient. Although a comparison with measured GFR should be necessary, choice of the estimation method needs caution in clinical decision-making and academic research.Horizon 2020 (H2020

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes