Algorithm for quantum-mechanical finite-nuclear-mass variational calculations of atoms with two p electrons using all-electron explicitly correlated Gaussian basis functions

A new algorithm for calculating the Hamiltonian matrix elements with all-electron explicitly correlated Gaussian functions for quantum-mechanical calculations of atoms with two p electrons or a single d electron have been derived and implemented. The Hamiltonian used in the approach was obtained by rigorously separating the center-of-mass motion and it explicitly depends on the finite mass of the nucleus. The approach was employed to perform test calculations on the isotopes of the carbon atom in their ground electronic states and to determine the finite-nuclear-mass corrections for these state

Algorithm for quantum-mechanical finite-nuclear-mass variational calculations of atoms with two p electrons using all-electron explicitly correlated Gaussian basis functions

A new algorithm for calculating the Hamiltonian matrix elements with all-electron explicitly correlated Gaussian functions for quantum-mechanical calculations of atoms with two p electrons or a single d electron have been derived and implemented. The Hamiltonian used in the approach was obtained by rigorously separating the center-of-mass motion and it explicitly depends on the finite mass of the nucleus. The approach was employed to perform test calculations on the isotopes of the carbon atom in their ground electronic states and to determine the finite-nuclear-mass corrections for these state

Molecular and epigenetic markers as promising tools to quantify the effect of occupational exposures and the risk of developing non-communicable diseases

Non-communicable diseases (NCDs) are chronic diseases that are by far the leading cause of death in the world. Many occupational hazards, together with social, economic and demographic factors, have been associated to NCDs development. Genetic susceptibility or environmental exposures alone are not usually sufficient to explain the pathogenesis of NCDs, but can be integrated in a more complex scenario that can result in pathological phenotypes. Epigenetics is a crucial component of this scenario, as its changes are related to specific exposures, therefore potentially able to display the effects of environment on the genome, filling the gap between genetic asset and environment in explaining disease development. To date, the most promising biomarkers have been assessed in occupational cohorts as well as in case/control studies and include DNA methylation, histone modifications, microRNA expression, extracellular vesicles, telomere length, and mitochondrial alterations

Treatment with fibrates is associated with higher LAL activity in dyslipidemic patients

Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesteryl esters (CE) and triglycerides (TG) within the lysosomes; generated cholesterol and free fatty acids (FFA) are released in the cytosol where they can regulate their own synthesis and metabolism. When LAL is not active, as in case of genetic mutations, CE and TG accumulate in the lysosomal compartment, while the lack of release of cholesterol and FFA in the cytosol leads to an upregulation of their synthesis. Thus, LAL plays a central role in the intracellular homeostasis of lipids. Since there are no indications about the effect of different lipid-lowering agents on LAL activity, aim of the study was to address the relationship between LAL activity and the type of lipid-lowering therapy in a cohort of dyslipidemic patients. LAL activity was measured on dried blood spot from 120 patients with hypercholesterolemia or mixed dyslipidemia and was negatively correlated to LDL-cholesterol levels. Among enrolled patients, ninety-one were taking one or more lipid-lowering drugs, as statins, fibrates, ezetimibe and omega-3 polyunsaturated fatty acids. When patients were stratified according to the type of lipid-lowering treatment, i.e. untreated, taking statins or taking fibrates, LAL activity was significantly higher in those with fibrates, even after adjustment for sex, age, BMI, lipid parameters, liver function, metabolic syndrome, diabetes and statin use. In a subset of patients tested after 3 months of treatment with micronized fenofibrate, LAL activity raised by 21%; the increase was negatively correlated with baseline LAL activity. Thus, the use of fibrates is independently associated with higher LAL activity in dyslipidemic patients, suggesting that the positive effects of PPAR-\u3b1 activation on cellular and systemic lipid homeostasis can also include an improved LAL activity

Prevalence, risk factors and outcomes of patients coming from the community with sepsis due to multidrug resistant bacteria

Background: Although previous studies showed an increasing prevalence of infections due to multi-drug resistant (MDR) bacteria in the community, specific data on sepsis are lacking. We aimed to assess prevalence, risk factors and outcomes of patients with sepsis due to MDR bacteria. Methods: An observational, retrospective study was conducted on consecutive adult patients coming from the community and admitted to the Policlinico Hospital, Milan, Italy, with a diagnosis of sepsis between January 2011 and December 2015. Primary study outcome was in-hospital mortality. Results: Among 518 patients, at least one MDR bacteria was isolated in 88 (17%). ESBL+ Enterobacteriaceae were the most prevalent MDR bacteria (9.7%) followed by MRSA (3.9%). Independent risk factors for sepsis due to MDR bacteria were septic shock (OR: 2.2; p = 0.002) and hospitalization in the previous 90 days (OR: 2.3; p = 0.003). Independent risk factors for sepsis due to ESBL+ bacteria were hospitalization in the previous 90 days (OR: 2.1; p = 0.02) and stroke (OR: 2.1; p = 0.04). A significantly higher mortality was detected among patients with vs. without MDR bacteria (40.2% vs. 23.1% respectively, p = 0.001). Independent risk factors for mortality among patients with sepsis were coagulation dysfunction (OR: 3.2; p = 0.03), septic shock (OR: 3.2; p = 0.003), and isolation of a MDR bacteria (OR: 4.6; p < 0.001). Conclusion: In light of the prevalence and impact of MDR bacteria causing sepsis in patients coming from the community, physicians should consider ESBL coverage when starting an empiric antibiotic therapy in patients with specific risk factors, especially in the presence of septic shock

A proteomic approach to identify novel disease biomarkers in LCAT deficiency

Genetic LCAT deficiency is a rare recessive autosomal disease due to loss-of-function mutations in the gene coding for the enzyme lecithin:cholesterol acyltransferase (LCAT). Homozygous carriers are characterized by corneal opacity, haemolytic anaemia and renal disease, which represent the first cause of morbidity and mortality in these subjects. Diagnostic and prognostic markers capable of early detecting declining kidney function in these subjects are not available, and the specific serum or urine proteomic signature of LCAT deficient carriers has never been assessed. Taking advantage of a proteomic approach, we performed 2-DE analysis of carriers' plasma and identified proteins present at different concentration in samples from homozygous carriers. Our data confirm the well-known alterations in the concentration of circulating apolipoproteins, with a statistically significant decrease of both apoA-I and apoA-II and a statistically significant increase of apoC-III. Furthermore, we observed increased level of alpha-1-antitrypsin, zinc-alpha-2-glycoprotein and retinol-binding protein 4, and reduced level of clusterin and haptoglobin. Interestingly, only beta but not alpha subunit of haptoglobin is significant reduced in homozygous subjects. Despite the limited sample size, our findings set the basis for assessing the identified protein in a larger population and for correlating their levels with clinical markers of renal function and anaemia. Significance: This investigation defines the effects of LCAT deficiency on the level of the major plasma proteins in homozygous and heterozygous carriers. Increase for some proteins, with different function, together with a drop for haptoglobin, and specifically for haptoglobin beta chains, are reported for the first time as part of a coherent signature. We are glad to have the opportunity to report our findings on this subject, which is one of the main interests for our research group, when Journal of Proteomics celebrates its 10th anniversary. With its various sections devoted to different areas of research, this journal is a privileged forum for publishing proteomic investigations without restrictions either in sample type or in technical approach. It is as well a privileged forum for reviewing literature data on various topics related to proteomics investigation, as colleagues in our research group have done over the years; by the way, a good share of the reviewed papers were as well reports published in Journal of Proteomics itself. The journal also offers opportunities for focused surveys through thematic issues devoted to a variety of subjects, timely selected for their current relevance in research; it was an honour for colleagues in our group to recently act as editors of one of those. Out of this diverse experience, we express our appreciation for the endeavour of Journal of Proteomics in its first 10 years of life \u2013 and wish identical and possibly greater success for the time to come

A Multi-Center Study Investigating Long COVID-19 in Healthcare Workers from North-Eastern Italy: Prevalence, Risk Factors and the Impact of Pre-Existing Humoral Immunity—ORCHESTRA Project

: Introduction: The impact of long-COVID-19 syndrome is rather variable, since it is influenced by several residual confounders. This study aimed to investigate the prevalence of long COVID-19 in healthcare workers (HCWs) from four university hospitals in north-eastern Italy: Trieste, Padua, Verona, and Modena-Reggio Emilia. Methods: During the period June 2022-August 2022, HCWs were surveyed for past COVID-19 infections, medical history, and any acute as well as post-COVID-19 symptoms. The prevalence of long COVID-19 was estimated at 30-60 days or 61+ days since first negative swab following first and second COVID-19 episode. Furthermore, the risk of long COVID-19 was investigated by multivariable logistic regression. Results were expressed as the adjusted odds ratio (aOR) with a 95% confidence interval (95%CI). Results: 5432 HCWs returned a usable questionnaire: 2401 were infected with SARS-CoV-2 at least once, 230 were infected at least twice, and 8 were infected three times. The prevalence of long COVID-19 after a primary COVID-19 infection was 24.0% at 30-60 days versus 16.3% at 61+ days, and 10.5% against 5.5% after the second SARS-CoV-2 event. The most frequent symptoms after a first COVID-19 event were asthenia (30.3%), followed by myalgia (13.7%), cough (12.4%), dyspnea (10.2%), concentration deficit (8.1%), headache (7.3%), and anosmia (6.5%), in decreasing order of prevalence. The risk of long COVID-19 at 30-60 days was significantly higher in HCWs hospitalized for COVID-19 (aOR = 3.34; 95%CI: 1.62; 6.89), those infected with SARS-CoV-2 during the early pandemic waves-namely the Wuhan (aOR = 2.16; 95%CI: 1.14; 4.09) or Alpha (aOR= 2.05; 95%CI: 1.25; 3.38) transmission periods-and progressively increasing with viral shedding time (VST), especially 15+ days (aOR = 3.20; 95%CI: 2.07; 4.94). Further determinants of long COVID-19 at 30-60 days since primary COVID-19 event were female sex (aOR = 1.91; 95%CI: 1.30; 2.80), age >40 years, abnormal BMI, or administrative services (reference category). In contrast, HCWs vaccinated with two doses before their primary infection (aOR = 0.57; 95%CI: 0.34; 0.94), undergraduate students, or postgraduate medical trainees were less likely to experience long COVID-19 at 30-60 days. Apart from pandemic waves, the main determinants of long COVID-19 at 30-60 days were confirmed at 61+ days. Conclusions: The risk of long COVID-19 following primary infection increased with the severity of acute disease and VST, especially during the initial pandemic waves, when more virulent viral strains were circulating, and susceptibility to SARS-CoV-2 was higher since most HCWs had not been infected yet, COVID-19 vaccines were still not available, and/or vaccination coverage was still building up. The risk of long COVID-19 therefore decreased inversely with humoral immunity at the individual level. Nevertheless, the prevalence of long COVID-19 was remarkably lower after SARS-CoV-2 reinfections regardless of vaccination status, suggesting that hybrid humoral immunity did not increase protection against the syndrome compared to immunity mounted by either natural infection or vaccination separately. Since the risk of long COVID-19 is currently low with Omicron and patients who developed the syndrome following SARS-CoV-2 infection in the early pandemic waves tend to return to a state of full health with time, a cost-effective approach to screen post-COVID-19 symptoms during the Omicron time could be restricted to vulnerable individuals developing severe disease and/or with prolonged VST

Effect of soy on metabolic syndrome and cardiovascular risk factors : a randomized controlled trial

Background: Cardiovascular diseases are currently the commonest cause of death worldwide. Different strategies for their primary prevention have been planned, taking into account the main known risk factors, which include an atherogenic lipid profile and visceral fat excess. Methods: The study was designed as a randomized, parallel, single-center study with a nutritional intervention duration of 12 weeks. Whole soy foods corresponding to 30 g/day soy protein were given in substitution of animal foods containing the same protein amount. Results: Soy nutritional intervention resulted in a reduction in the number of MetS features in 13/26 subjects. Moreover, in the soy group we observed a significant improvement of median percentage changes for body weight ( 121.5 %) and BMI ( 121.5 %), as well as for atherogenic lipid markers, namely TC ( 124.85 %), LDL-C ( 125.25 %), non-HDL-C ( 127.14 %) and apoB ( 1214.8 %). Since the majority of the studied variables were strongly correlated, three factors were identified which explained the majority (52 %) of the total variance in the whole data set. Among them, factor 1, which loaded lipid and adipose variables, explained the 22 % of total variance, showing a statistically significant difference between treatment arms (p = 0.002). Conclusions: The inclusion of whole soy foods (corresponding to 30 g/day protein) in a lipid-lowering diet significantly improved a relevant set of biomarkers associated with cardiovascular risk

HDL-mediated cholesterol efflux and plasma loading capacities are altered in subjects with metabolically-but not genetically driven non-alcoholic fatty liver disease (NAFLD)

Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (-18.6%; p < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically-vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically-vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (−18.6%; p < 0.001) as well as that mediated by cholesterol transporters (−25.3% ABCA1; −16.3% ABCG1; −14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired