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Introduction and objectives. Secondary bacterial infections (SBIs) contribute to worse in-hospital outcomes in patients with Coronavirus disease 2019 (COVID-19). Treatment with proton pump inhibitors (PPIs) is associated with an increased risk of bacterial infections in different clinical settings. However, the association between PPI treatment prior to hospital admission and the occurrence of either SBIs or secondary bacterial sepsis (SBS) as well as their joint impact on clinical outcomes of patients hospitalized for COVID-19 are not clarified.Patients and methods. We retrospectively analyzed preadmission PPI use, in-hospital occurrence of SBIs and SBS, and in-hospital outcomes of a cohort of patients hospitalized for COVID-19.Results. Among 1087 patients, 447 (41%) were on PPI treatment prior to hospital admission. During the hospital stay, 197 (18%) and 223 (20%) patients were diagnosed with SBIs and SBS, respectively. The composite endpoint of intensive care unit (ICU) admission/in‐hospital death was met by 214 (20%) patients. Preadmission PPI treatment was independently associated with up to a 2.1-fold and 1.7-fold increased risk of SBIs and SBS, respectively. The occurrence of SBS was independently associated with up to a 2.2-fold increased risk of ICU admission/in-hospital death. A significant preadmission PPI treatment x SBS interaction emerged in predicting ICU admission/in-hospital death (F = 5.221, pinteraction = 0.023).Conclusions. PPI treatment prior to hospital admission for COVID-19 is associated with an increased risk of SBIs and SBS. In addition, it interacts with SBS in predicting in-hospital prognosis. An appropriate use of PPIs may attenuate the risk of adverse clinical outcomes during hospitalization for COVID-19.

Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima–media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54–79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima–media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent.

Introduction Influenza virus infection is associated with high morbidity and mortality, and so additional therapeutic strategies to reduce the burden for healthcare systems are needed. Statins, by virtue of their anti-inflammatory and immunomodulatory effects, have been hypothesized as capable of influencing the host’s response against the influenza virus. The aim of this meta-analysis was to assess the effect of ongoing statin treatment on susceptibility to influenza virus infection and on influenza-associated mortality. Material and methods Studies investigating the impact of statin treatment on influenza prevalence and mortality were searched for in the PubMed-Medline, Scopus, ISI Web of Knowledge, Embase, Proquest, OVID, EBSCO, and CINAHL databases (up to 8 November 2021). Fixed- and random-effects models and the generic inverse variance method were used for quantitative data synthesis. Results In the meta-analysis of 14 arms of 2 eligible studies, including 14,997 flu-vaccinated and unvaccinated patients, treatment with statins was associated with a reduction of influenza virus prevalence (odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.73–0.99; p = 0.040). No significant effect of statins on the susceptibility to influenza infection was observed in the distinct communities of either vaccinated or unvaccinated subjects. Among 9 arms of 6 eligible studies, including 87,204 patients, the use of statins among patients with influenza was associated with a reduced mortality (OR = 0.68, 95% CI: 0.56, 0.82; p < 0.001). This result was confirmed for both 30-day mortality since influenza infection diagnosis (OR = 0.61, 95% CI: 0.47, 0.80; p

Abstract Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin‐associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3–5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)—what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real‐world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step‐by‐step patient‐centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long‐term compliance with lipid‐lowering therapy.

BackgroundSpore Trap is an environmental detection technology, already used in the field of allergology to monitor the presence and composition of potentially inspirable airborne micronic bioparticulate. This device is potentially suitable for environmental monitoring of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in hospital, as well as in other high-risk closed environments. The aim of the present study is to investigate the accuracy of the Spore Trap system in detecting SARS-CoV-2 in indoor bioaerosol of hospital rooms.MethodsThe Spore Trap was placed in hospital rooms hosting patients with documented SARS-CoV-2 infection (n = 36) or, as a negative control, in rooms where patients with documented negativity to a Real-Time Polymerase Chain Reaction molecular test for SARS-CoV-2 were admitted (n = 10). The monitoring of the bioaerosol was carried on for 24 h. Collected samples were analyzed by real-time polymerase chain reaction.ResultsThe estimated sensitivity of the Spore Trap device for detecting SARS-CoV-2 in an indoor environment is 69.4% (95% C.I. 54.3-84.4%), with a specificity of 100%.ConclusionThe Spore Trap technology is effective in detecting airborne SARS-CoV-2 virus with excellent specificity and high sensitivity, when compared to previous reports. The SARS-CoV-2 pandemic scenario has suggested that indoor air quality control will be a priority in future public health management and will certainly need to include an environmental bio-investigation protocol.

BackgroundChronic systemic inflammation reduces the bioavailability of circulating endothelial progenitor cells (EPCs). Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme of immune tolerance catalyzing the initial step of tryptophan degradation along the so-called l-kynurenine (l-kyn) pathway, that is induced by inflammatory stimuli and exerts anti-inflammatory effects. A specific relationship between IDO1 activity and circulating EPC numbers has not yet been investigated.MethodsIn this study, circulating EPCs were examined in mice treated with low doses of lipopolysaccharide (LPS) to mimic low-grade inflammation. Moreover, the association between IDO1 activity and circulating EPCs was studied in a cohort of 277 patients with variable systemic low-grade inflammation.ResultsRepeated low doses of LPS caused a decrease in circulating EPCs and l-kyn supplementation, mimicking IDO1 activation, significantly increased EPC numbers under homeostatic conditions preventing EPC decline in low-grade endotoxemia. Accordingly, in patients with variable systemic low-grade inflammation, there was a significant interaction between IDO1 activity and high-sensitivity C-reactive protein (hs-CRP) in predicting circulating EPCs, with high hs-CRP associated with significantly lower EPCs at low IDO1 activity but not at high IDO1 activity.InterpretationOverall, these findings demonstrate that systemic low-grade inflammation reduces circulating EPCs. However, high IDO1 activity and l-kyn supplementation limit circulating EPC loss in low-grade inflammation.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid metabolism contributing to cardiovascular (CV) risk in the general population. The relationship between PCSK9 and CV risk in systemic autoimmune diseases has been poorly explored. We investigated the association between plasma PCSK9, measures of immune–inflammatory status and markers of atherosclerosis in 52 consecutive patients with primary Sjögren’s syndrome (pSS) in comparison to healthy controls (HCs). Median plasma PCSK9 levels were significantly higher in pSS patients versus HCs (162 (79–255) vs. 53 (39–99) ng/mL). Significantly higher prevalence of subclinical atherosclerosis and lower of dyslipidaemia (61% vs. 85%, p = 0.042) characterized pSS patients versus HCs. In pSS, no significant correlation emerged between PCSK9 and disease activity, atherosclerosis and lipid levels. In HCs, PCSK9 significantly correlated with lipid levels and atherosclerosis. Interestingly, significantly higher PCSK9 levels were found in HCs with high-to-very-high as compared to low-to-moderate CV risk (p = 0.018) while a non-significant trend towards higher PCSK9 levels was detected in pSS patients with low-to-moderate as compared to high-to-very-high CV risk (p = 0.060). This is the first demonstration that pSS patients, despite lower prevalence of dyslipidaemia and higher CV risk profile, are characterized by a 3-fold increase in PCSK9 levels in comparison to HCs. As PCSK9 does not correlate with measures of CV risk, its role in CV morbidity in pSS needs further investigation.

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.

Abstract Statins are a family of drugs that are used for treating hyperlipidaemia with a recognized capacity to prevent cardiovascular disease events. They inhibit β‐hydroxy β‐methylglutaryl‐coenzyme A reductase, i.e. the rate‐limiting enzyme in mevalonate pathway, reduce endogenous cholesterol synthesis, and increase low‐density lipoprotein clearance by promoting low‐density lipoprotein receptor expression mainly in the hepatocytes. Statins have pleiotropic effects including stabilization of atherosclerotic plaques, immunomodulation, anti‐inflammatory properties, improvement of endothelial function, antioxidant, and anti‐thrombotic action. Despite all beneficial effects, statins may elicit adverse reactions such as myopathy. Studies have shown that mitochondria play an important role in statin‐induced myopathies. In this review, we aim to report the mechanisms of action of statins on mitochondrial function. Results have shown that statins have several effects on mitochondria including reduction of coenzyme Q10 level, inhibition of respiratory chain complexes, induction of mitochondrial apoptosis, dysregulation of Ca2+ metabolism, and carnitine palmitoyltransferase‐2 expression. The use of statins has been associated with the onset of additional pathological conditions like diabetes and dementia as a result of interference with mitochondrial pathways by various mechanisms, such as reduction in mitochondrial oxidative phosphorylation, increase in oxidative stress, decrease in uncoupling protein 3 concentration, and interference in amyloid‐β metabolism. Overall, data reported in this review suggest that statins may have major effects on mitochondrial function, and some of their adverse effects might be mediated through mitochondrial pathways.

Abstract Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.

Abstract Background Low-density lipoprotein cholesterol (LDL-C) causes atherosclerotic disease, as demonstrated in experimental and epidemiological cohorts, randomised controlled trials, and Mendelian randomisation studies. Main text There is considerable inconsistency between existing guidelines as to how to effectively manage patients at low overall risk of cardiovascular disease (CVD) who have persistently elevated levels of LDL-C. We propose a step-by-step practical approach for the management of cardiovascular risks in individuals with low ( 140 mg/dL, 3.6 mmol/L) LDL-C. The strategy proposed is based on the level of adherence to lifestyle interventions (LSI), and in case of non-adherence, stepwise practical management, including lipid-lowering therapy, is recommended to achieve a target LDL-C levels (

Abstract Apoptotic cells are rapidly engulfed and degraded by phagocytes through efferocytosis. Efferocytosis is a highly regulated process. It is triggered upon the activation of caspase-dependent apoptosis, which in turn promotes the expression of “eat me” signals on the surface of dying cells and the release of soluble “find me” signals for the recruitment of phagocytes. To date, many “eat me” signals have been recognized, including phosphatidylserine (PS), intercellular adhesion molecule-3, carbohydrates (e.g., amino sugars, mannose) and calreticulin. Among them, PS is the most studied one. PS recognition receptors are different functionally active receptors expressed by phagocytes. Various PS recognition receptors with different structure, cell type expression, and ability to bind to PS have been recognized. Although PS recognition receptors do not fall into a single classification or family of proteins due to their structural differences, they all share the common ability to activate downstream signaling pathways leading to the production of anti-inflammatory mediators. In this review, available evidence regarding molecular mechanisms underlying PS recognition receptor-regulated clearance of apoptotic cells is discussed. In addition, some efferocytosis-independent biological functions of PS recognition receptors are reviewed.

Solar energy has a significant potential for future power generation but its intermittent and variable nature results in fluctuations of the operational performance of solar power plants. Despite thermal energy storage (TES) systems improving the flexibility and the sustainability of the performance of Concentrated Solar Power (CSP) plants, smart management is required to deal with the complex dynamic variations in the behaviour and interaction of the different plant's subsystems. In this paper, the design, manufacture, and validation of a smart control unit with extended capabilities for a small-scale CSP combined heat and power (CHP) system are described. More precisely, the control unit has been designed to control and optimise the operation of a micro-scale Organic Rankine Cycle (ORC) unit coupled with Linear Fresnel Reflectors solar field and an advanced latent heat thermal energy storage tank which were developed by a consortium of universities and companies in the framework of the EU-funded project “Innova Microsolar”.In parallel to the designing and building the smart control unit, an advanced simulator has been developed in Matlab/Simulink® to investigate the performance of the plant for a wide range of varying ambient and operating conditions. The simulation framework has been connected to the real control unit according to a hardware-in-the-loop (HiL) approach to optimise the control logic of the integrated plant to overcome potential technical and reliability issues during the commissioning of the plant. The developed hardware and the proposed scientific approach can be extended to a wide range of complex solar energy systems equipped with TES and to be integrated into the built environment.

Background The association between elevated serum uric acid (SUA), cardiovascular disease (CVD) risk, and carotid atherosclerosis has long been explored, and contrasting results have been reported. Therefore, the role of SUA as an independent risk factor for vascular events (VEs) and carotid atherosclerosis deserves further attention. We investigated the relationship between SUA, incident VEs, carotid intima‐media thickness (cIMT), and cIMT progression in subjects at moderate‐to‐high CVD risk. Methods and Results In the IMPROVE (IMT‐Progression as Predictors of VEs) study, 3686 participants (median age 64 years; 48% men) with ≥ 3 vascular risk factors, free from VEs at baseline, were grouped according to SUA quartiles (division points: 244–284–328 µmol/L in women, 295–336–385 µmol/L in men). Carotid‐IMT and its 15‐month progression, along with incident VEs, were recorded. A U‐shaped association between SUA and VEs was observed in men, with 2.4‐fold (P = 0.004) and 2.5‐fold (P = 0.002) increased CVD risk in the first and fourth SUA quartiles as compared with the second. Adjusted hazard ratios (HRs) for cerebro‐VEs in men were the highest (first and fourth quartile versus second: HR, 5.3, P = 0.010 and HR, 4.4, P = 0.023, respectively). SUA level was independently associated with cIMT progression in men (β = 0.068, P = 0.014). No significant association between SUA levels, CVD end points, and cIMT progression were found in women. Conclusions Both low and high SUA levels are associated with an increased risk of VEs in men at moderate‐to‐high CVD risk but not in women. Only elevated SUA levels predict cIMT progression and at a lesser but not significant extent in women.

In this work a hardware-in-the-loop (HiL) simulator of a novel micro combined heat and power system is presented and its use for control algorithm optimization is demonstrated and discussed. The plant under investigation consists of a concentrated Linear Fresnel Reflectors solar field, a 2 kWe/18 kWt Organic Rankine Cycle unit and an advanced latent heat thermal energy storage tank equipped with reversible heat pipes as developed by a consortium of universities and companies within the EU funded project Innova Microsolar. A smart control unit manages their integration and monitors the operation of each subsystem.In order to support the optimization of the control algorithms and the definition of the best control strategy of the micro-CHP plant at different working conditions, a simulation framework based on Matlab/Simulink has been developed by the authors and connected to the real control unit according to a HiL approach. Ad-hoc models of the different subsystems together with those of the components (i.e. valves and variable speed pumps) regulating the plant operation have been included.The use of the HiL simulator has permitted to optimize the control logic of the integrated plant prior to its future commissioning, thus helping to overcome some of the technical and reliability issues occurring during the setup of the real system. In particular, the HiL has allowed: (i) to define the proportional and integral gains of the diverters in order to assure a robust and fast response of the plant during the switch among the different operation modes; (ii) to prove the limits of acting on the oil pump flow rate in assuring the nominal oil temperature at the inlet of the ORC unit, due to the inherent fluctuations caused by this control strategy; and (iii) to assess the best control strategy which is obtained by acting on the aperture of the diverter which controls the oil mass flow rate to the ORC unit. Hence, the scientific approach here proposed can be extended also to many other complex energy conversion systems in order to significantly reduce the potential critical issues during their commissioning.

Background: Variable sex-disaggregated data on Coronavirus disease 2019 (COVID-19) incidence proportion (IP) have been reported in different datasets and studies. Factors explaining the inconsistent distribution of COVID-19 among sexes are still unclear. Objectives: This study aimed to analyse time-related variation of sex-disaggregated COVID-19 IP in Italy since March 9th to May 11th 2020, and to test its association with the frequency of swab testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Study design: Sex-disaggregated data on COVID-19 cases were collected from Italian publicly accessible databases along with undisaggregated data on the number of reverse transcriptase–polymerase chain reaction (RT-PCR) SARS-CoV-2 tests. Crude and adjusted associations between the frequency of RT-PCR SARS-CoV-2 testing and male-to-female (M/F) ratio of COVID-19 IP were performed. Results: COVID-19 IP increased progressively in both sexes. Sex prevalence of COVID-19 IP reversed over time, with the M/F ratio of COVID-19 IP having passed from 1,73 to 0,91. The mean number of daily swabs for RT-PCR SARS-CoV-2 test increased progressively until reaching a plateau in the last three weeks of the study period. The M/F ratio of COVID-19 IP inversely correlated with the number of daily swabs for RT-PCR SARS-CoV-2 test (r = -0,87, p < 0.001), even after adjusting for the median age of COVID-19 cases (β = -0,66, p < 0,001). Conclusions: Time-related changes of sex distribution of COVID-19 IP in Italy are strongly influenced by the number of swabs testing for SARS-CoV-2. Whether gender-related disparities in the access to the diagnosis of COVID-19 may explain such a result need to be explored.

Acute inflammation has been described as a reactive dynamic process, promoted by the secretion of proinflammatory mediators, including lipid molecules like leukotrienes and prostaglandins, and counterbalanced by proresolving mediators including omega-3 polyunsaturated fatty-acid- (PUFA-) derived molecules. The switch from the initiation to the resolution phase of acute inflammatory response is crucial for tissue homeostasis, whereas the failure to resolve early inflammation by specialized proresolving mediators leads to chronic inflammation and tissue damage. Among PUFA-derived proresolving mediators, different eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derivatives have been described, namely, resolvins (resolution phase interaction products), which exert their anti-inflammatory and immune-regulatory activities through specific G-protein-coupled receptors. In recent years, compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in different neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. This review summarizes current knowledge on the role of resolvins in resolution of inflammation and highlights available evidence showing the neuroprotective potential of EPA- and DHA-derived resolvins (E-series and D-series resolvins, respectively) in neurodegenerative diseases.

(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54–79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.

Solar energy is widely recognized as one of the most attractive renewable energy sources to support the transition toward a decarbonized society. Use of low- and medium-temperature concentrated solar technologies makes decentralized power production of combined heating and power (CHP) an alternative to conventional energy conversion systems. However, because of the changes in solar radiation and the inertia of the different subsystems, the operation control of concentrated solar power (CSP) plants is fundamental to increasing their overall conversion efficiency and improving reliability. Therefore, in this study, the operation control of a micro-scale CHP plant consisting of a linear Fresnel reflector solar field, an organic Rankine cycle unit, and a phase change material thermal energy storage tank, as designed and built under the EU-funded Innova Microsolar project by a consortium of universities and companies, is investigated. In particular, a fuzzy logic control is developed in MATLAB/Simulink by the authors in order to (i) initially recognize the type of user according to the related energy consumption profile by means of a neural network and (ii) optimize the thermal-load-following approach by introducing a set of fuzzy rules to switch among the different operation modes. Annual simulations are performed by combining the plant with different thermal load profiles. In general, the analysis shows that that the proposed fuzzy logic control increases the contribution of the TES unit in supplying the ORC unit, while reducing the number of switches between the different OMs. Furthermore, when connected with a residential user load profile, the overall electrical and thermal energy production of the plant increases. Hence, the developed control logic proves to have good potential in increasing the energy efficiency of low- and medium-temperature concentrated solar ORC systems when integrated into the built environment.

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax; cIMTmean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.

Apoptosis happens continuously for millions of cells along with the active removal of apoptotic debris in order to maintain tissue homeostasis. In this respect, efferocytosis, i.e., the process of dead cell clearance, is orchestrated through cell exposure of a set of “find me,” “eat me,” and “tolerate me” signals facilitating the engulfment of dying cells through phagocytosis by macrophages and dendritic cells. The clearance of dead cells via phagocytes is of utmost importance to maintain the immune system tolerance to self-antigens. Accordingly, this biological activity prevents the release of autoantigens by dead cells, thus potentially suppressing the undesirable autoreactivity of immune cells and the appearance of inflammatory autoimmune disorders as systemic lupus erythematous and rheumatoid arthritis. In the present study, the apoptosis pathways and their immune regulation were reviewed. Moreover, efferocytosis process and its impairment in association with some autoimmune diseases were discussed.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS), and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs), typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs). In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A), known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001). Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+) T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

This paper reports on a 71-year-old Caucasian male who underwent neurosurgery for an oligodendroglioma, followed by a cranial-sinus fistula and cerebrospinal fluid rhinorrhea. The clinical course was complicated due to an extensively drug-resistant Acinetobacter baumannii meningitis. The patient was treated with colistin methanesulfonate, intrathecal for 24 days and intravenous for 46 days. In addition, the patient received meropenem and teicoplanin to treat a bacterial aspiration pneumonia, probably caused by methicillin resistant Staphylococcus aureus and multi drug-resistant Klebiesella pneumoniae. Cerebrospinal fluid trough colistin levels resulted above the MIC of A. baumannii. Colistin cerebrospinal fluid accumulation over the treatment period was not reported. Meningitis was cured and A. baumannii eradicated. No side effects from the antimicrobial therapy were observed. In conclusion, this case highlights the issues in treating infections caused by resistant Gram-negative bacteria and supports previous findings on the efficacy, pharmacokinetic and tolerability of intravenous and intrathecal colistin treatments.