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Diagnostic criteria of malnutrition phenotypes have been recently updated. Uncovering the prevalence of these conditions in patients undergoing hip replacement may be crucial in order to apply the most appropriate diagnostic-therapeutic paths to the right patient at the right time. Sixty patients aged between 60 and 85 undergoing elective hip replacement were recruited. Preoperative measures concerning eating behaviors, anthropometry, physical performance, laboratory parameters, and patient reported measures of pain and function were collected, used to make diagnosis, and explored whether they differed based on malnutrition categorization. Patients undernourished were 18.75%, sarcopenic 13.34%, sarcopenic obesity 4.26%, and 8.88% undernourished and sarcopenic. Well-nourished patients ate more cereals and meat, exhibited lower white blood cells but higher lymphocytes, and reported greater hip-related pain. One in three older patients undergoing elective hip replacement was malnourished. Eating behaviors and leucocytes were the discriminating factors between malnourished and well-nourished. It remains to be established whether malnutrition affects outcome after surgery.

Statins have improved the potential to prevent cardiovascular disease events and to prolong the lives of patients. Statins, among the most widely used drugs worldwide, reduce the levels of low-density lipoprotein cholesterol (LDL-C) by an average of 30–50%. However, non-adherence to statin therapy, due to statin intolerance, might be as high as 60% after 24 months of treatment and is associated with a 70% increase in the risk of cardiovascular disease events. Statin intolerance can be classified as a complete inability to tolerate any dose of a statin or a partial intolerance with the inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. Reasons for discontinuation are many, with statin-associated muscle symptoms being cited as the most frequent reason for stopping therapy and the incidence of muscle symptoms increasing with treatment intensity. Considering the causal effect of LDL-C in the atherosclerotic process, clinicians should consider that regardless of the lipid-lowering drugs patients are willing to take, any reduction in LDL-C they achieve will afford them some benefit in reducing cardiovascular risk. Besides statins, the current therapeutic armamentarium offers different strategies to reach LDL-C targets in statin-intolerant patients (i.e. a fixed combination between a lower dose of statin plus ezetimibe, bempedoic acid, or proprotein convertase subtilisin/kexin type 9 inhibition).

Elucidating antibody–antigen complexes at the atomic level is of utmost interest for understanding immune responses and designing better therapies. Cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for mapping protein–protein interactions, suggesting valuable structural insights. However, the use of XL-MS studies to enable epitope/paratope mapping of antibody–antigen complexes is still limited up to now. XL-MS data can be used to drive integrative modeling of antibody–antigen complexes, where cross-links information serves as distance restraints for the precise determination of binding interfaces. In this approach, XL-MS data are employed to identify connections between binding interfaces of the antibody and the antigen, thus informing molecular modeling. Current literature provides minimal input about the impact of XL-MS data on the integrative modeling of antibody–antigen complexes. Here, we applied XL-MS to retrieve information about binding interfaces of three antibody–antigen complexes. We leveraged XL-MS data to perform integrative modeling using HADDOCK (active-passive residues and distance restraints strategies) and AlphaLink2. We then compared these three approaches with initial predictions of investigated antibody–antigen complexes by AlphaFold Multimer. This work emphasizes the importance of cross-linking data in resolving conformational dynamics of antibody–antigen complexes, ultimately enhancing the design of better protein therapeutics and vaccines.

The volume plasmon modes of a confined electron gas are engineered in a step-like semiconductor potential, which induces the formation of adjacent regions of different charge density. Each region supports spatially localized collective modes. Adjacent modes are theoretically demonstrated to couple, forming delocalized modes, which are well-described with a hybridization picture. Exploiting the thin-film Berreman effect, the engineered plasmon modes are directly observed in optical measurements. Using a quantum microscopic theory, the asymmetry of the single-particle electronic states is shown to be directly imprinted on the nonuniform polarization of the collective modes.

We report room temperature heterodyne detection of a quantum cascade laser beaten with a local oscillator on a unipolar quantum photodetector in two different atmospheric windows, at 4.8 µm and 9 µm. A noise equivalent power of few pW is measured by employing an active stabilization technique in which the local oscillator and the signal are locked in phase. The measured heterodyne noise equivalent power is six orders of magnitude lower than that obtained with direct detection.

Mechanical forces induced by high-speed oscillations provide an elegant way to dynamically alter the fundamental properties of materials such as refractive index, absorption coefficient and gain dynamics. Although the precise control of mechanical oscillation has been well developed in the past decades, the notion of dynamic mechanical forces has not been harnessed for developing tunable lasers. Here we demonstrate actively tunable mid-infrared laser action in group-IV nanomechanical oscillators with a compact form factor. A suspended GeSn cantilever nanobeam on a Si substrate is resonantly driven by radio-frequency waves. Electrically controlled mechanical oscillation induces elastic strain that periodically varies with time in the GeSn nanobeam, enabling actively tunable lasing emission at >2 μm wavelengths. By utilizing mechanical resonances in the radio frequency as a driving mechanism, this work presents wide-range mid-infrared tunable lasers with ultralow tuning power consumption.

Optoelectronic devices rely on conductive layers as electrodes, but they usually introduce optical losses that are detrimental to the device performances. While the use of transparent conductive oxides is established in the visible region, these materials show high losses at longer wavelengths. Here, we demonstrate a photodiode based on a metallic grating acting as an electrode. The grating generates a multiresonant photonic structure over the diode stack and allows strong broadband absorption. The obtained device achieves the highest performances reported so far for a midwave infrared nanocrystal-based detector, with external quantum efficiency above 90%, detectivity of 7 × 1011Jones at 80 K at 5 μm, and a sub-100 ns time response. Furthermore, we demonstrate that combining different gratings with a single diode stack can generate a bias reconfigurable response and develop new functionalities such as band rejection.

The unique and multifaceted properties of high-density lipoproteins (HDL)—ranging from cholesterol efflux and reverse transport to anti-inflammatory, antioxidant, and immunomodulatory effects—have prompted its direct use, particularly in cardiovascular ischemic conditions.

• In the Italian male elite Under-19 football Championship, each Club can expect around 15 non-contact muscle injuries during the season (for a team of 25 players) distributed as follows: 6 hamstrings, 3 quadriceps, 2 adductors, 2 calf and 1 iliopsoas muscle injuries.

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.

Irisin is a circulating myokine released from skeletal muscles after physical exercise. Irisin production decreases during the course of chronic kidney disease (CKD) as a potential consequence of sarcopenia and physical inactivity.

The solar photo-Fenton process leads to the formation of transformation products (TPs) that are new compounds with an unknown chemical, physical, and biological characteristics. There are no commercial analytical standards for these new TPs. Due to this difficulty, ecotoxicity studies have been able to provide only limited information, while intrinsic features of the samples (such as complexity and matrix effects), as well as issues related to the sensitivity of the test organism, can further hinder investigations in cases where TPs coexist in mixtures. However, a viable option is to carry out in silicostudies that do not use analytical standards or living organisms and do not require long testing periods to reach endpoints. In the present work, 90 chemical compounds (pharmaceuticals and their TPs generated by the solar photo-Fenton process) were evaluated using freely available software to assess the following endpoints: biodegradability, carcinogenicity, mutagenicity, and PBT (persistence, bioaccumulation, and toxicity). Chemometric analyses (HCA and PCA) were also applied to enhance the interpretation of the results. The main findings were that flutamide, chloramphenicol, and nimesulide, together with their TPs, were mostly non-biodegradable compounds that could be potentially mutagenic and carcinogenic. Therefore, these drugs and their TPs should not be released into the environment. The results indicated that it could be important to improve the solar photo-Fenton process or to couple this Advanced Oxidation Process with additional physicochemical treatment in order to efficiently remove these organic microcontaminants.

The objective of this paper is to compare two methods of airport capacity analysis: Static Analysis and Dynamic Analysis. For this purpose, the two methods have been evaluated in two different scenarios, the first one related to normal operations and the other to an exceptional event. In the context of the coronavirus COVID-19 pandemic, they can be considered as coinciding with a "Pre-Covid" and a "Covid" scenario. Currently, the calculation of airport capacity is mostly linked to static analysis, a solid historical method, based on empirical formulas dictated by the International Air Transport Association (IATA). The dynamic analysis is a state-of-the-art method that uses software packages to simulate a great variety of non-ordinary situations by incorporating a wide range of information related to the specific case study such as airport layout, entry/exit routes, etc. Nevertheless, since it does not currently have specific guidelines, is still little used. The following study evaluates the two methods, highlighting their strengths and weaknesses.

Purpose: The effects of growth hormone (GH) replacement on bone mass and body composition in adult with GH deficiency (AGHD) are still debated with regard to their persistence in the long term. Moreover, the impact of the gender on the response to GH is controversial. Aim of this study was to evaluate the long-term effects of rhGH replacement on bone mass and body composition in a monocentric cohort of patients with AGHD. Methods: Data from 118 patients with AGHD (34.8 ± 14.4 years, 43 women and 75 men) treated with rhGH for a period of at least 3 years up to a maximum of 10 were retrospectively collected. Bone mineral density (BMD) at the lumbar spine, femur, and 1/3 radius, and total and truncular body composition were evaluated by dual-energy X-ray absorption (DXA) before and during treatment. Clinical and laboratory evaluations were performed before and during the treatment period on an annual basis. Results: Lumbar spine BMD consistently increased in males, while it decreased in females after a transient improvement observed during the first 4 years of therapy. There were no significant changes in femoral and 1/3 radial BMD in either sexes. Lean mass significantly increased in both sexes, while fat mass only decreased in males. Conclusions: In AGHD patients long-term rhGH replacement therapy induces a positive effect with regard to bone mass and body composition. A sexual dimorphism in the response to treatment is evident, with males displaying a more favorable outcome.

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Dyslipidaemias and in particular elevated plasma low-density lipoprotein cholesterol (LDL-C) levels are major risk factors for atherosclerotic cardiovascular disease (ASCVD). Indeed, the more LDL-C is reduced the larger will be the ASCVD risk reduction. Although statins represent the first-line intervention to reduce the atherosclerotic burden driven by raised levels of LDL-C, adherence is not optimal and most patients do not follow guidelines and recommended doses. Thus, to achieve optimal LDL-C goals, especially in very high-risk patients, there is a need for new and safe agents, more tolerable than statins with low risk of myalgia. Thus, the present review will address the most recent clinical trials with bempedoic acid and inclisiran. Bempedoic acid is an oral drug acting at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and not associated with muscular side effects. Inclisiran, the first-in-class small interfering RNA-based approach, has the ability to effectively reduce LDL-C by inhibiting the hepatic synthesis of proprotein convertase subtilisin/kexin type 9, with the advantage of requiring subcutaneous of a single dose on Day 1, Day 90, and every 6 months thereafter.

Nanocrystals (NCs) have gained considerable attention for their broadly tunable absorption from the UV to the THz range. Nevertheless, their optical features suffer from a lack of tunability once integrated into optoelectronic devices. Here, we show that bias tunable aspectral response is obtained by coupling a HgTe NC array with a plasmonic resonator. Up to 15 meV blueshift can be achieved from a 3 μm absorbing wavelength structure under a 3 V bias voltage when the NC exciton is coupled with a mode of the resonator. We demonstrate that the blueshift arises from the interplay between hopping transport and inhomogeneous absorption due to the presence of the photonic structure. The observed tunable spectral response is qualitatively reproduced in simulation by introducing a bias-dependent diffusion length in the charge transport. This work expands the realm of existing NC-based devices and paves the way toward light modulators.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), mainly synthetized and released by the liver, represents one of the key regulators of low-density lipoprotein cholesterol. Although genetic and interventional studies have demonstrated that lowering PCSK9 levels corresponds to a cardiovascular benefit, identification of non–cholesterol-related processes has emerged since its discovery. Besides liver, PCSK9 is also expressed in many tissues (eg, intestine, endocrine pancreas, and brain). The aim of the present review is to describe and discuss PCSK9 pathophysiology and possible non–lipid-lowering effects whether already extensively characterized (eg, inflammatory burden of atherosclerosis, triglyceride-rich lipoprotein metabolism, and platelet activation), or to be unraveled (eg, in adipose tissue). The identification of novel transcriptional factors in the promoter region of human PCSK9 (eg, ChREBP) characterizes new mechanisms explaining how controlling intrahepatic glucose may be a therapeutic strategy to reduce cardiovascular risk in type 2 diabetes. Finally, the evidence describing PCSK9 as involved in cell proliferation and apoptosis raises the possibility of this protein being involved in cancer risk.

It is essential to develop a safety culture with the participation of university teachers and students in actions and studies that can contribute to safer and more sustainable practices in academic laboratories. The present work analyzes the potential of a training program to raise awareness and establish environmental education and green chemistry concepts concerning procedures for the management and treatment of chemical waste generated in experimental classes. This is a qualitative case study providing a critical perspective of environmental education. The training activity, lasting 45 minutes, was conducted with 66 students entering Chemistry courses at a Brazilian public university. Data collection was carried out using an initial questionnaire to identify the students’ prior knowledge, and a final one applied after the training period. The questionnaires contained open questions and closed questions with a Likert-type scale. The results showed that the training activity contributed to the students’ understanding of the concepts, procedures, and attitudes related to the management and treatment of chemical waste, including the interrelations among the environmental, social, and economic impacts of waste management, the importance of correct separation and storage of residues for disposal using different types of treatment, the civil liability of the academic community for the residues generated, and how the 3Rs principles can favor sustainable practices in the academic context.

AbstractGrowth performance and meat quality traits of 24 Massese suckling lambs reared up to 69 days of age in different farming systems were evaluated. Three groups were considered: stall (S) reared indoors and fed concentrate and hay; pasture (P) reared outdoor and fed pasture and hay; semi free-range (F) reared indoors during the night and at pasture during the day, fed concentrate, hay and herbage. The lambs remained constantly with their dams for the whole period, having thus always access to mothers’ milk. Animals weights were recorded, and, after slaughtering, carcase traits were considered. Fatty acids composition and chemical/physical parameters of milk and meat were analysed. Lambs growth was similar in the first 30 days, while afterwards differences emerged: P lambs recorded the worst values reaching slaughter weight of 14.6 kg versus 22.3 and 22.7 of the S and the F group, respectively. Carcase of P lambs resulted less fat and with a lower lean/bone ratio than the other groups (1.8, 2.1 and 2.3 for P, S and F, respectively). Fatty acids composition of ewes’ milk had effect on lambs’ meat profile, probably because they continued to suck milk until slaughter. Moreover, also farming system affected fatty acids profile of lambs’ meat: grazing animals, especially P, showed the highest PUFA and the lowest SFA percentage and P meat showed the best composition for human health. As regards physical traits, F meat was more coloured than P and S meat, while P meat was less tender than others.HighlightsTwo-month-old Massese lamb is a marketable product.Suckled milk affected lambs’ meat composition also at later ages.Pasture in lambs’ diet increases PUFA content in the meat.

Despite the demonstrated benefits of statins and injectable biologics, there is a need for new and safe oral agents for addressing classical lipid targets, low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). LDL-C is unquestionably causal in the development of atherogenesis and atherosclerotic cardiovascular disease, but new options are required to address triglyceride-rich lipoproteins and lipoprotein(a). For hypercholesterolaemia, pitavastatin provides a very low dose and potent statin that does not adversely affect glucose metabolism; bempedoic acid acts at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and is not associated with muscular side effects. For hypertriglyceridaemia, pemafibrate displays a unique and selective agonist activity on peroxisomal proliferator activated receptor-α that does not elevate homocysteine or creatinine. Although omega-3 fatty acids supplementation is not effective in secondary prevention, high dose eicosapentaenoic ethyl ester can lead to a remarkable fall in first and recurrent events in high risk patients with hypertriglyceridaemia/low HDL-C. Gemcabene, a dicarboxylic acid regulating apolipoprotein B-100, is effective in reducing both cholesterol and triglycerides. Among cholesteryl ester transfer protein antagonists that elevate HDL-C, only anacetrapib reduces cardiovascular events. Probucol stimulates reverse cholesteryl ester transport, lowers LDL-C stabilizing plaques and may lower incidence of cardiovascular events. These agents, which act through novel mechanisms, afford good and potentially safe treatment choices that may increase adherence and the attainment of therapeutic targets.

Plasmons in heavily doped semiconductor layers are optically active excitations with sharp resonances in the 5–15 μm wavelength region set by the doping level and the effective mass. Here, we demonstrate that volume plasmons can form in doped layers of widths of hundreds of nanometers, without the need of potential barrier for electronic confinement. Their strong interaction with light makes them perfect absorbers and therefore suitable for incandescent emission. Moreover, by injecting microwave current in the doped layer, we can modulate the temperature of the electron gas. We have fabricated devices for high frequency thermal emission and measured incandescent emission up to 50 MHz, limited by the cutoff of our detector. The frequency-dependent thermal emission is very well reproduced by our theoretical model that let us envision a frequency cutoff in the tens of GHz.

Many photonic and plasmonic structures have been proposed to achieve ultrasubwavelength light confinement across the electromagnetic spectrum. Notwithstanding this effort, however, the efficient funneling of external radiation into nanoscale volumes remains problematic. Here, we demonstrate a photonic concept that fulfills the seemingly incompatible requirements for both strong electromagnetic confinement and impedance matching to free space. Our architecture consists of antenna-coupled meta-atom resonators that funnel up to 90% of the incident radiation into an ultrasubwavelength semiconductor quantum well absorber of volume V= λ310–6. A significant fraction of the coupled electromagnetic energy is used to excite the electronic transitions in the quantum well, with a photon absorption efficiency 550 times larger than the intrinsic value of the electronic dipole. This system opens important perspectives for ultralow dark current quantum detectors and for the study of light–matter interaction in the extreme regimes of electronic and photonic confinement.

The contamination of aquatic systems by pharmaceuticals has received considerable attention in recent decades, because these substances are increasingly detected in the environment. This is due to the abundant use of pharmaceuticals by the population and, consequently, their constant introduction into aquatic systems through domestic, industrial, and hospital wastewaters. Hospital effluents have highly complex compositions and present potential toxicity towards the environment. In this work, a screening methodology was developed to evaluate the occurrence of pharmaceutical products in hospital wastewater, using a viable, easy, and economical strategy employing commercial pharmaceutical compounds for screening analysis. Six samplings of hospital wastewater were carried out monthly (from winter until summer). The samples were filtered and pre-concentrated/extracted using solid phase extraction (SPE). The pharmaceuticals screening procedure required the construction of two databases, one for each ionization mode (positive and negative), which contained information that allowed the identification of the presence of these pharmaceuticals in the studied samples. Commercial pharmaceutical compounds were used as analytical standards. Based on this strategy and, using liquid chromatography coupled to high resolution mass spectrometry, it was possible to screen 110 pharmaceuticals and, from these, to confirm the presence of 38 pharmaceuticals in analyzed samples. These results indicate the analytes that should be taken into account in the further development of quantitative methods for pharmaceutical analysis.

Thanks to their large sensitivity to electromagnetic fields, microelectromechanical systems are becoming attractive for applications in the THz band (0.1–10 THz). However, up to date all THz electromechanical systems couple electromagnetic fields to mechanical motion only through photothermal dissipative forces: such mechanism allows for sensitive detection but prevents applications that require coherent transfer of information. In this work, we present a THz electromechanical meta-atom where the coupling between an electromagnetic mode and the displacement of a metallic micro-beam is substantially controlled by a conservative Coulomb force due to charge oscillations in the nanometric-size capacitive part of the meta-atom. We present experiments, performed at room temperature, which allow distinguishing and precisely quantifying the contributions of conservative and dissipative forces in the operation of our electromechanical resonator. Our analysis shows that the Coulomb force becomes the dominant contribution of the total driving force for high-order mechanical modes. Such system paves the way for the realization of coherent THz to optical transducers and allows the realization of fundamental optomechanical systems in the THz frequency range.

Low testosterone levels are associated with an increased incidence of cardiovascular (CV) events, but the underlying biochemical mechanisms are not fully understood. The clinical condition of hypogonadism offers a unique model to unravel the possible role of lipoprotein-associated abnormalities in CV risk. In particular, the assessment of the functional capacities of high-density lipoproteins (HDLs) may provide insights besides traditional risk factors.

Regulation of pro-protein convertase subtilisin/kexin type 9 (PCSK9) by drugs has led to the development of a still small number of agents with powerful activity on low-density lipoprotein cholesterol levels, associated with a significant reduction of cardiovascular events in patients in secondary prevention. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) studies, with the two available PCSK9 antagonists, i.e. evolocumab and alirocumab, both reported a 15% reduction in major adverse cardiovascular events. Regulation of PCSK9 expression is dependent upon a number of factors, partly genetic and partly associated to a complex transcriptional system, mainly controlled by sterol regulatory element binding proteins. PCSK9 is further regulated by concomitant drug treatments, particularly by statins, enhancing PCSK9 secretion but decreasing its stimulatory phosphorylated form (S688). These complex transcriptional mechanisms lead to variable circulating levels making clinical measurements of plasma PCSK9 for cardiovascular risk assessment a debated matter. Determination of total PCSK9 levels may provide a diagnostic tool for explaining an apparent resistance to PCSK9 inhibitors, thus indicating the need for other approaches. Newer agents targeting PCSK9 are in clinical development with a major interest in those with a longer duration of action, e.g. RNA silencing, allowing optimal patient compliance. Interest has been expanded to areas not only limited to low-density lipoprotein cholesterol reduction but also investigating other non-lipid pathways raising cardiovascular risk, in particular inflammation associated to raised high-sensitivity C-reactive protein levels, not significantly affected by the present PCSK9 antagonists.

ABSTRACTIntroduction: Tolerability problems in treating hypercholesterolemic patients undergoing statin treatment are of growing concern to physicians and patients, thus underlining the need for an agent with a similar mechanism but minimal side effects. A drug with a somewhat similar mechanism to statins but free of muscular side effects is ETC-1002 (bempedoic acid). It inhibits cholesterol biosynthesis at a step preceding HMG-CoA reductase, i.e.ATP citrate lyase (ACLY). A prodrug, ETC-1002 is converted to the active agent only in liver, not in skeletal muscle, and this may prevent any myotoxic activity.Area covered: The mechanism of ETC-1002 activity is described in detail, considering that ACLY inhibition markedly attenuated atherosclerosis in animal models. Clinical studies are also reported. Expert opinion: Present day LDL-C lowering treatments lead to significant reductions of cardiovascular (CV) events but, at times, the need to interrupt statin treatment appears to be dangerous due to a rapid rise in CV risk. The excellent tolerability of ETC-1002 makes it a useful alternative, either alone or as an adjunct to ezetimibe, for patients with statin intolerance needing to achieve significant CV risk reduction. ETC-1002 is also associated with a marked fall in high-sensitivity C-reactive protein.

Aims Exposure to airborne particulate matter has been consistently associated with early death and increased morbidity, particularly raising the risk of cardiovascular disease. Obesity, one of the leading cardiovascular disease risk factors, increases susceptibility to the adverse effects of particulate matter exposure. Proprotein convertase subtilisin/kexin type 9 has been related to a large number of cardiovascular risk factors, e.g. atherogenic lipoproteins, arterial stiffness and platelet activation. Thus, the present study was aimed at evaluating, in a series of obese individuals, the effects of particulate matter less than 10 µm in diameter (PM10) on proprotein convertase subtilisin/kexin type 9 circulating levels.Methods and results In 500 obese subjects, participating in the cross-sectional Susceptibility to Particle Health Effects, miRNAs and Exosomes (SPHERE) study, we evaluated the effects of long- and short-term PM10exposure on circulating proprotein convertase subtilisin/kexin type 9 levels. In the studied individuals (body mass index: 33.3 ± 5.2 kg/m2) with an annual average PM10exposure of 40.12 ± 4.71 µg/m3, proprotein convertase subtilisin/kexin type 9 levels were 248.7 ± 78.6 ng/mL. In univariate analysis, PM10exposure (annual average) was associated with proprotein convertase subtilisin/kexin type 9 levels (β=1.83, standard error = 0.75, p= 0.014). Interestingly, in a multivariable linear regression model, this association was observed only for carriers of lower concentrations of interferon-γ, whereas it was lost in the presence of higher interferon-γ levels. Proprotein convertase subtilisin/kexin type 9 levels were positively associated with the Framingham Risk Score, which was raised by 15.8% for each 100 ng/ml rise of proprotein convertase subtilisin/kexin type 9.Conclusions In obese individuals, more sensitive to the damaging effects of environmental air pollution, PM10exposure positively associates with proprotein convertase subtilisin/kexin type 9 plasma levels especially in those with low levels of interferon-γ.

Trigger finger is one of the most frequent causes of hand pain and disability. Recently, an endoscopic trigger finger release technique was developed, but outcomes have rarely been reported. Here, we present the outcomes of 2154 endoscopic trigger finger release procedures in a single center.

The ubiquitous presence of antibiotics in aquatic ecosystems due to their frequent and indiscriminate use has become a major global health concern, leading to high environmental bacteria and resistance gene development. In this context, this study aimed to evaluate the degradation of three antibiotics, ciprofloxacin (CIP), sulfamethoxazole (SMX) and tetracycline (TET), employing a mining residue as the photocatalyst. The mining residue was characterized by the Brunauer-Emmett-Teller (BET), X ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X ray diffraction (XRD) techniques, and exhibited high iron content (~70%) predominantly Fe+2. A rotatable central composite design (RCCD) employing catalyst concentrations, H2O2and pH as variables was applied, resulting in optimal catalyst and H2O2concentrations of 277.01mgL-1and 65.37mgL-1, respectively, at pH 3.4. These conditions achieved 89 and 83% SMX and CIP degradation rates and the TET concentration at 60min of treatment was lower than the instrumental LOD, confirming the predominance of catalyst photo-Fenton reactions. When applied to a real effluent sample, 71 and 79% SMX and CIP degradation rates were observed, respectively, while no degradation value changes were noted for TET at 60min. The main reactive species involved in the antibiotic degradation reactions were HO•for SMX, O2•-and h+for CIP, and O2•-for TET. In total, 12 antibiotic transformation products (TPs) were identified by LC-QTOF MS. The most frequent TPs observed during antibiotic degradation were formed by hydroxylation, dealkylation, defluorination and hydrolysis of the sulfonamide bond. The investigated mining residue is, therefore, a low-cost and efficient alternative for the photocatalytic degradation of CIP, SMX and TET, contributing to the United Nations Sustainable Development Goals (SDG 6) and follows circular economy principles.

AbstractThe aim of this work was to determine the chemical, physical and sensorial characteristics of a cured product called ‘Cuore di Spalla’, resulting from two different pig genotypes (G) and two salting times (S). Fourteen Duroc × Large White (D × LW) and 14 Cinta Senese × Large White (CS × LW), reared in the same condition in outdoor and fed commercial mixture. The animals were slaughtered at 10 months of age which corresponds to an average live weight of 143 ± 15 kg for D × LW and 122 ± 15 kg for CS × LW. The right shoulders were salted for 3 days (L) and the left ones for 5 days (H). Physical (colour, texture profile analysis), chemical (moisture; crude protein; IMF; ash; salt; total lipids; fatty acids) and sensorial analyses (by panellists’ group) as well as volatile compounds profile (by SPME-GC-MS technique) were determined at the end of seasoning period. The genotype affected product’s size (1484.3 vs 1857.1 g of final weight for CS × LW and D × LW respectively), chemical characteristics and texture (cohesiveness 0.50 vs 0.53 and springiness 6.73 vs 7.12 for CS × LW and D × LW respectively). Aromatic profile was less affected by the factors considered or at least the panellists were not able to discriminate the effect. The main family of volatile compounds affected by genotype was alcohols. Salting time seemed to affect only the parameters closely related to salt (16.52 vs 15.33% of salt and 5.15 vs 4.35 for saltiness in H vs L respectively).HighlightsThe genotypes determined differences in size, fat quantity and physical-chemical parameters of the ‘Cuore di Spalla’ product.Very limited differences in the aromatic profile were found.Both salting times led to high salt content in the product.It seems feasible to produce the ‘Cuore di Spalla’ with further reduction of salting times.

Terahertz frequency metrology by radio frequency downconversion using femtosecond optical sampling relies on the harmonic factor retrieval between the terahertz frequency and the optical sampling rate. At typical femtosecond laser repetition rates, this imposes an ambiguity for frequency metrology. We report on a dual-comb sampling system for the unambiguous frequency measurement of terahertz quantum cascade lasers with hertz-level precision. Two Ti:sapphire oscillators with 10 GHz repetition rate are used for the electro-optic sampling of terahertz radiation at 2.5 THz emitted by actively mode-locked terahertz quantum cascade lasers with 9.7 GHz and 19.6 GHz repetition rates. By coherent downconversion, the emitted terahertz waveforms are measured in the radio frequency domain. The terahertz frequency comb is stabilized by employing a phase-locked loop on a radio frequency beat-note signal. A second infrared sampling comb is used to measure the absolute frequencies of the terahertz radiation. This method, which is based on the detuning of the sampling repetition rates, allows the direct retrieval of the quantum cascade laser’s absolute frequency in real time without using additional optical frequency references for calibration. In order to demonstrate the feasibility of the stabilization and readout technique, a high-resolution spectroscopy measurement on gaseous methanol is presented.

Room-temperature operation is essential for any optoelectronics technology that aims to provide low-cost, compact systems for widespread applications. A recent technological advance in this direction is bolometric detection for thermal imaging, which has achieved relatively high sensitivity and video rates (about 60 hertz) at room temperature. However, owing to thermally induced dark current, room-temperature operation is still a great challenge for semiconductor photodetectors targeting the wavelength band between 8 and 12 micrometres, and all relevant applications, such as imaging, environmental remote sensing and laser-based free-space communication, have been realized at low temperatures. For these devices, high sensitivity and high speed have never been compatible with high-temperature operation. Here we show that a long-wavelength (nine micrometres) infrared quantum-well photodetector fabricated from a metamaterial made of sub-wavelength metallic resonators exhibits strongly enhanced performance with respect to the state of the art up to room temperature. This occurs because the photonic collection area of each resonator is much larger than its electrical area, thus substantially reducing the dark current of the device. Furthermore, we show that our photonic architecture overcomes intrinsic limitations of the material, such as the drop of the electronic drift velocity with temperature, which constrains conventional geometries at cryogenic operation. Finally, the reduced physical area of the device and its increased responsivity allow us to take advantage of the intrinsic high-frequency response of the quantum detector at room temperature. By mixing the frequencies of two quantum-cascade lasers on the detector, which acts as a heterodyne receiver, we have measured a high-frequency signal, above four gigahertz (GHz). Therefore, these wide-band uncooled detectors could benefit technologies such as high-speed (gigabits per second) multichannel coherent data transfer and high-precision molecular spectroscopy.

Regional innovation systems (RISs) are increasingly emerging in less developed areas. Based on the case study of the mechatronic cluster in the Italian southern region, Apulia, this paper analyses how institutions have managed to promote the establishment of a RIS in disadvantaged areas. Through a longitudinal analysis over more than half a century, the Apulian case study shows that the creation of this RIS in less developed areas is the result of a dynamic process characterised by a multi-level governance, initially promoted by the central government through a top-down logic, and then integrated by action of local actors through a bottom-up approach. A key role is played by the regionalisation of innovation policies and by the strategic action of regional public institutions to promote the interaction among enterprises and universities. Our analysis highlights that several ingredients should simultaneously occur for a regional innovation policy to be effective. Any regional innovation strategy significantly lacking one of these core pre-conditions and ingredients is risky. Policy-makers should carefully study the opportunities and challenges arising from local contexts before embarking in ambitious place-based innovation strategies.

In recent years, Brazil has been one of the largest consumers of pesticides in the world, with atrazine (ATZ) being an active principle often used in Brazilian agriculture. In this context, this study is aimed at developing a fast, simple and economical routine methodology for the identification and quantification of ATZ and its transformation products, deisopropylatrazine (DIA) and deethylatrazine (DEA), by using dispersive liquid–liquid microextraction (DLLME) as the extraction technique associated with gas chromatography-mass spectrometry (GC/MS) analysis in surface water (class 2 river). The best extraction conditions were set using the Doehlert experimental design. Validation of the developed DLLME-GC/MS methodology showed limits of detection and quantification of 0.050 and 0.150 μg L−1for ATZ, 0.250 and 0.500 μg L−1for DEA and 0.250 and 0.900 μg L−1for DIA, respectively. Parameters such as the matrix effect, repeatability and recovery were evaluated. The proposed method proved to be simple, easy and cost-effective for the analysis of a large number of different types of aqueous samples.

ABSTRACTIntroduction: Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction.Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e.g., WY14,643). Original publications in English were selected, as well as Abstracts of international meetings’ presentations. Clinical trials were identified using the clinicaltrial.gov database and the EU Clinical Trials Register (clinicaltrialsregister.eu).Expert opinion: In addition to the aim of improving lipid profile with fibrates, the interest in new PPAR-α activators stems from the need to overcome some of the clinical problems encountered with dose-dependent adverse events; a rise of plasma creatinine, gallstone formation, drug-drug interactions (i.e. gemfibrozil), and myopathy. New PPAR-α agonists improved TG and HDL-C levels as well as other parameters related to TG metabolism (remnant cholesterol and apoB), without raising liver enzymes. Although the use of fibrates is rated ‘second choice’ by many clinicians, new PPAR-α agonists may offer a more accessible route to the management of hypertriglyceridemia, a frequent clinical condition.

Background: Cardiovascular risk (CV) factors associated with the metabolic syndrome (MetS) may vary in different populations. In some, hypertension may be the major determinant, in others are low high-density lipoprotein cholesterol (HDL-C), high triglycerides, or another component. Subjects and Methods: Subjects included in this analysis were identified in 2006, among those attending the Lipid Clinic of the Niguarda Hospital, and followed up through to 2013. Patient characteristics (including the occurrence of CV events) were obtained from electronic medical records. MetS was diagnosed according to the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) guidelines. The carotid intima media thickness (cIMT) was also followed in these patients over the years. Results: After 7 years a total of 858 subjects had a complete follow-up; 271 of those had MetS. Patients developing a CV event showed elevated baseline cIMT (e.g. cIMTmax ≥2.4 mm in males and ≥2.2 mm in females); moreover the cIMT in MetS patients was higher at baseline and the rise over 7 years was larger compared with patients without MetS. By examining each body variable for MetS we found that a waist to height ratio (WHtR) ≥0.5 was present in nearly all subjects with a CV event. Conclusion: The follow-up data of a series of Italian patients with and without MetS, clearly indicates that the former have a raised cIMT and their arterial IMT progression is greater and the presence of a larger WHtR is apparently linked to a higher incidence of CV events.