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Short-term unloading experienced following injury or hospitalisation induces muscle atrophy and weakness. The effects of exercise following unloading have been scarcely investigated. We investigated the functional and molecular adaptations to a resistance training (RT) programme following short-term unloading. Eleven males (22.09 ± 2.91 years) underwent 10 days of unilateral lower limb suspension (ULLS) followed by 21 days of knee extensor RT (three times/week). Data collection occurred at Baseline (LS0), after ULLS (LS10) and at active recovery (AR21). Knee extensor maximum voluntary contraction (MVC) was evaluated. Quadriceps volume was estimated by ultrasonography. Muscle fibre cross-sectional area, fibre type distribution, glycogen content and succinate dehydrogenase (SDH) activity were measured from vastus lateralis biopsies. Mitochondrial-related proteins were quantified by western blot and transcriptional responses were assessed by RNA sequencing. Following ULLS, quadriceps volume and MVC decreased significantly (3.7%, P < 0.05; 29.3%, P < 0.001). At AR21 (vs. LS10), MVC was fully restored (42%) and quadriceps volume increased markedly (18.6%, P < 0.001). Glycogen content and whole-body water increased at AR21 (14%, P < 0.001; 3.1%, P < 0.05). We observed a marked increase in fibre type I at AR21 (38%, P < 0.05). SDH immunoreactivity increased significantly after exercise (20%, P < 0.001). Mitochondrial fusion (MFN1, MFN2 and OPA1) and fission (DRP1) proteins were markedly increased by RT, and the most differentially expressed genes belonged to oxidative phosphorylation pathways. In contrast with what is usually observed after RT, oxidative metabolism, slow fibre type and mitochondrial dynamics were enhanced beyond expected. We propose that prior exposure to short-term muscle unloading may drive the nature of molecular adaptations to subsequent RT. KEY POINTS: Short-term unloading is often experienced during recovery from injuries and hospitalisation, leading to loss of muscle mass and strength. Although exercise can be beneficial in mitigating/reversing such alterations during disuse, only a few studies have focused on the effects of exercise following muscle unloading. With an integrative physiological approach, we aimed to elucidate the basic mechanisms of muscle function recovery in response to 21 days of resistance exercise that followed 10 days of unilateral lower limb suspension (ULLS), assessing whether the mechanisms underlying recovery are defined by a specific reversal of those that occurred during disuse. Resistance training was successful in recovering functional and structural muscle properties after 10 days of ULLS, but in contrast with what is usually observed in response to this training modality, oxidative metabolism and slow fibre type were mostly enhanced. We propose that prior exposure to short-term muscle unloading may drive the adaptations to subsequent exercise., (© 2025 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Purpose: to investigate the early consequences of type 1 diabetes (T1D) on the neural strategies of muscle force production., Methods: motor unit (MU) activity was recorded from the vastus lateralis muscle with High-Density surface Electromyography during isometric knee extension at 20 and 40% of maximum voluntary contraction (MVC) in 8 T1D (4 males, 4 females, 30.5 ± 3.6 years) and 8 matched control (4 males, 4 females, 27.3 ± 5.9 years) participants. Muscle biopsies were also collected from vastus lateralis for fiber type analysis, including myosin heavy chain (MyHC) isoform content via protein and mRNA expression., Results: MVC was comparable between groups as well as MU conduction velocity, action potentials' amplitude and proportions of MyHC protein isoforms. Nonetheless, MU discharge rate, relative derecruitment thresholds and mRNA expression of MyHC isoform I were lower in T1D., Conclusions: young people with uncomplicated T1D present a different neural control of muscle force production. Furthermore, differences are detectable non-invasively in absence of any functional manifestation (i.e., force production and fiber type distribution). These novel findings suggest that T1D has early consequences on the neuromuscular system and highlights the necessity of a better characterization of neural control in this population., Competing Interests: Declarations. Conflic of interest: None., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

14 C measurements on the carbonaceous fractions of atmospheric aerosol are an important tool for source apportionment. In this paper, a 14 C-based source apportionment study was carried out on samples collected during winter 2021 at an urban background site in the Po Valley, one of the main pollution hot-spot areas in Europe. The samples were prepared using MISSMARPLE (MIlan Small-SaMple Automated Radiocarbon Preparation LinE for atmospheric aerosol), a recently developed sample preparation line for 14 C measurements on atmospheric aerosol carbon fractions, specifically targeting small samples (about 50 μgC). 14 C-based source apportionment was performed separately for elemental carbon (EC) and organic carbon (OC), after suitable optimization of model parameters. As this is the first source apportionment study using MISSMARPLE-prepared samples, our results were compared with other tracers and source apportionment outcomes obtained through parallel methodologies, demonstrating strong correlations in all tests (R > 0.87). The source apportionment results showed that fossil fuel combustion remains the main source of EC in the investigated area (60%), while modern contributions generally dominate the OC fraction (66%). However, some episodes were identified where fossil fuel combustion was the dominant contributor also to the OC fraction (up to 66%). During these episodes, the importance of secondary OC formation from fossil fuel combustion was highlighted through the EC-tracer approach. Thus, fossil fuel combustion is still a significant source of carbonaceous aerosol in the Po Valley during the winter. Both primary emissions and gaseous precursors must be targeted by future abatement policies to effectively reduce pollution in the area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age-related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties., Methods: We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants., Results: Thirty-nine older individuals were non-sarcopenic (NS), 31 pre-sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross-sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P < 0.0001). Handgrip force and the Short Physical Performance Battery score also showed a diminishing trend. iEMG analyses revealed elevated near fibre segment jitter in NS, PS and S compared with Y (Y vs. NS and S: P < 0.0001; Y vs. PS: P = 0.0169), suggestive of age-related impaired NMJ transmission. Increased C-terminal agrin fragment (P < 0.0001) and altered caveolin 3 protein expression were consistent with age-related NMJ instability in all the older groups. The iMUNE was lower in all older groups (P < 0.0001), confirming age-related loss of MUs. An age-related increase in MU potential complexity was also observed. These observations were accompanied by increased muscle denervation and axonal damage, evinced by the increase in neural cell adhesion molecule-positive fibres (Y vs. NS: P < 0.0001; Y vs. S: P = 0.02) and the increase in serum concentration of neurofilament light chain (P < 0.0001), respectively. Notably, most of these MU and NMJ parameters did not differ when comparing older individuals with or without sarcopenia., Conclusions: Alterations in MU properties, axonal damage, an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system. These neuromuscular alterations are accompanied by muscle wasting and weakness; however, they appear to precede clinically diagnosed sarcopenia, as they are already detectable in older NS individuals., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Behçet's disease is an inflammatory condition, caused by vasculitis of big and small veins and arteries in which, although vascular inflammation is the basis of disease, cardiac involvement is rare. We present a rare case of a man, affected by Behçet's disease, with pulmonary embolism due to a floating thrombus in the right ventricle., Case Summary: We report a case of a 36-year-old man admitted to emergency department due to dyspnoea and haemoptysis. He had already been diagnosed with Behçet's disease, and he was in therapy with low doses of azathioprine and prednisone from three months. Thorax CT scan detected pulmonary embolism with pulmonary infraction. No evidence of deep vein thrombosis was found. The echocardiogram pointed out a floating mass of at least 30 mm in the right ventricle. Cardiac magnetic resonance confirmed the diagnosis of right ventricle thrombosis. On the hypothesis of an inflammatory genesis of the thrombosis, immunosuppressive drugs and anticoagulation with vitamin K antagonist were prescribed. The patient underwent echocardiograms every 3 weeks, and the mass disappeared 5 months later., Discussion: Behçet's disease is a systemic inflammatory disorder that often affects vessels and rarely the heart. Thrombosis can be the only clinical feature of primary or relapsing events with also atypical origin site. Thrombosis suggests a high inflammatory status that needs to be balanced with the right immunosuppressive therapy, associated to anticoagulation., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Prior evidence has shown that neural factors contribute to the loss of muscle force after skeletal muscle disuse. However, little is known about the specific neural mechanisms altered by disuse. Persistent inward current (PIC) is an intrinsic property of motoneurons responsible for prolonging and amplifying the synaptic input, proportionally to the level of neuromodulation, thus influencing motoneuron discharge rate and force production. Here, we hypothesized that short-term unilateral lower limb suspension (ULLS) would reduce the neuromodulatory input associated with PIC, contributing to the reduction of force generation capacity. In addition, we tested whether physical exercise would restore the force generation capacity by reestablishing the initial level of neuromodulatory input., Methods: In 12 young adults, we assessed maximal voluntary contraction pre- and post-10 d of ULLS and after 21 d of active recovery (AR) based on resistance exercise. PIC was estimated from high-density surface electromyograms of the vastus lateralis muscle as the delta frequency (Δ F ) of paired motor units calculated during isometric ramped contractions., Results: The values of Δ F were reduced after 10 d of ULLS (-33%, P < 0.001), but were fully reestablished after the AR (+29.4%, P < 0.001). The changes in estimated PIC values were correlated ( r = 0.63, P = 0.004) with the reduction in maximal voluntary contraction after ULLS (-29%, P = 0.002) and its recovery after the AR (+28.5%, P = 0.003)., Conclusions: Our findings suggest that PIC estimates are reduced by muscle disuse and may contribute to the loss of force production and its recovery with exercise. Overall, this is the first study demonstrating that, in addition to peripheral neuromuscular changes, central neuromodulation is a major contributor to the loss of force generation capacity after disuse, and can be recovered after resistance exercise., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

A randomized control trial was conducted to assess the effectiveness of progressive muscle relaxation and deep breathing exercises on pain, disability, and sleep quality among patients with chronic tension-type headache. Of the 169 randomly selected patients, 84 performed the intervention and reported less pain severity and disability and better sleep quality after 12 weeks., Competing Interests: No conflict of interest among authors to be declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The role of N-glycosylation in the myogenic process remains poorly understood. Here, we evaluated the impact of N-glycosylation inhibition by Tunicamycin (TUN) or by phosphomannomutase 2 (PMM2) gene knockdown, which encodes an enzyme essential for catalyzing an early step of the N-glycosylation pathway, on C2C12 myoblast differentiation. The effect of chronic treatment with TUN on tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of WT and MLC/mIgf-1 transgenic mice, which overexpress muscle Igf-1Ea mRNA isoform, was also investigated. TUN-treated and PMM2 knockdown C2C12 cells showed reduced ConA, PHA-L, and AAL lectin binding and increased ER-stress-related gene expression (Chop and Hspa5 mRNAs and s/uXbp1 ratio) compared to controls. Myogenic markers (MyoD, myogenin, and Mrf4 mRNAs and MF20 protein) and myotube formation were reduced in both TUN-treated and PMM2 knockdown C2C12 cells. Body and TA weight of WT and MLC/mIgf-1 mice were not modified by TUN treatment, while lectin binding slightly decreased in the TA muscle of WT (ConA and AAL) and MLC/mIgf-1 (ConA) mice. The ER-stress-related gene expression did not change in the TA muscle of WT and MLC/mIgf-1 mice after TUN treatment. TUN treatment decreased myogenin mRNA and increased atrogen-1 mRNA, particularly in the TA muscle of WT mice. Finally, the IGF-1 production and IGF1R signaling pathways activation were reduced due to N-glycosylation inhibition in TA and EDL muscles. Decreased IGF1R expression was found in TUN-treated C2C12 myoblasts which was associated with lower IGF-1-induced IGF1R, AKT, and ERK1/2 phosphorylation compared to CTR cells. Chronic TUN-challenge models can help to elucidate the molecular mechanisms through which diseases associated with aberrant N-glycosylation, such as Congenital Disorders of Glycosylation (CDG), affect muscle and other tissue functions., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Particulate Matter (PM) is a complex and heterogeneous mixture of atmospheric particles recognized as a threat to human health. Oxidative Potential (OP) measurement is a promising and integrative method for estimating PM-induced health impacts since it is recognized as more closely associated with adverse health effects than ordinarily used PM mass concentrations. OP measurements could be introduced in the air quality monitoring, along with the parameters currently evaluated. PM deposition in the lungs induces oxidative stress, inflammation, and DNA damage. The study aimed to compare the OP measurements with toxicological effects on BEAS-2B and THP-1 cells of winter and summer PM 1 collected in the Po Valley (Italy) during 2021. PM 1 was extracted in deionized water by mechanical agitation and tested for OP and, in parallel, used to treat cells. Cytotoxicity, genotoxicity, oxidative stress, and inflammatory responses were assessed by MTT test, DCFH-DA assay, micronucleus, γ-H2AX, comet assay modified with endonucleases, ELISA, and Real-Time PCR. The evaluation of OP was performed by applying three different assays: dithiothreitol (OP DTT ), ascorbic acid (OP AA ), and 2',7'-dichlorofluorescein (OP DCFH ), in addition, the reducing potential was also analysed (RP DPPH ). Seasonal differences were detected in all the parameters investigated. The amount of DNA damage detected with the Comet assay and ROS formation highlights the presence of oxidative damage both in winter and in summer samples, while DNA damage (micronucleus) and genes regulation were mainly detected in winter samples. A positive correlation with OP DCFH (Spearman's analysis, p < 0.05) was detected for IL-8 secretion and γ-H2AX. These results provide a biological support to the implementation in air quality monitoring of OP measurements as a useful proxy to estimate PM-induced cellular toxicological responses. In addition, these results provide new insights for the assessment of the ability of secondary aerosol in the background atmosphere to induce oxidative stress and health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to non-invasively test the hypothesis that (a) short-term lower limb unloading would induce changes in the neural control of force production (based on motor units (MUs) properties) in the vastus lateralis muscle and (b) possible changes are reversed by active recovery (AR)., Methods: Ten young males underwent 10 days of unilateral lower limb suspension (ULLS) followed by 21 days of AR. During ULLS, participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position (15°-20°) and with the contralateral foot raised by an elevated shoe. The AR was based on resistance exercise (leg press and leg extension) and executed at 70% of each participant's 1 repetition maximum, 3 times/week. Maximal voluntary isometric contraction (MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline, after ULLS, and after AR. MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%, 25%, and 50% of the current MVC, and individual MUs were tracked across the 3 data collection points., Results: We identified 1428 unique MUs, and 270 of them (18.9%) were accurately tracked. After ULLS, MVC decreased by 29.77%, MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities (with changes between the 2 variables strongly correlated), while discharge rate was reduced at 10% and 25% but not at 50% MVC. Impaired MVC and MUs properties fully recovered to baseline levels after AR. Similar changes were observed in the pool of total as well as tracked MUs., Conclusion: Our novel results demonstrate, non-invasively, that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs, suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold. However, after 21 days of AR, the impaired MUs properties were fully restored to baseline levels, highlighting the plasticity of the components involved in neural control., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023. Production and hosting by Elsevier B.V.)

High-Density surface Electromyography (HD-sEMG) is the most established technique for the non-invasive analysis of single motor unit (MU) activity in humans. It provides the possibility to study the central properties (e.g., discharge rate) of large populations of MUs by analysis of their firing pattern. Additionally, by spike-triggered averaging, peripheral properties such as MUs conduction velocity can be estimated over adjacent regions of the muscles and single MUs can be tracked across different recording sessions. In this tutorial, we guide the reader through the investigation of MUs properties from decomposed HD-sEMG recordings by providing both the theoretical knowledge and practical tools necessary to perform the analyses. The practical application of this tutorial is based on openhdemg, a free and open-source community-based framework for the automated analysis of MUs properties built on Python 3 and composed of different modules for HD-sEMG data handling, visualisation, editing, and analysis. openhdemg is interfaceable with most of the available recording software, equipment or decomposition techniques, and all the built-in functions are easily adaptable to different experimental needs. The framework also includes a graphical user interface which enables users with limited coding skills to perform a robust and reliable analysis of MUs properties without coding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Many patients who access in the emergency department for acute bleeding are on anticoagulants; before specific reversal agents were developed, bleeding on anticoagulants was burdened with a substantial increase in morbidity and mortality. Clinical trials demonstrated favourable risk-benefit profiles of direct-acting oral anticoagulants compared with vitamin K antagonists in patients with atrial fibrillation and compared with low molecular weight heparin in patients treated and prevented from venous thromboembolism. Even if they drastically reduced some types of bleeding, particularly intracranial haemorrhage, they have not completely eliminated this risk. The arrival of a patient with active bleeding in the emergency department is always a critical scenario that involves resources and costs. In critical setting, the diagnosis and treatment of bleeding should occurred simultaneously. Understanding the pathophysiological mechanisms that occur during bleeding is essential for establish the most appropriate therapies and improve the standard of care of the haemorrhagic patients., Competing Interests: Conflict of interest: All authors declare that they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives: Pulmonary embolism (PE) has a major burden of morbidity and mortality, consequently the need for a prompt risk stratification for these subjects is crucial. In order to evaluate the risk management and final disposition of patients with PE in the Emergency Department (ED), we conducted a study that was divided in two phases: Phase I retrospective study (RS), Phase II prospective study (PS)., Materials and Methods: In Phase I, 291 patients were enrolled while in Phase II, 83 subjects were evaluated. In both study phases, the enrolled subjects were analyzed for final disposition in ED using PESI score, right ventricle (RV) imaging, and high-sensitive cardiac troponin I (hs-cTnI) data. The RS patients were divided into low risk and high risk according to the sPESI score, while PS patients were grouped in low, intermediate, and high risk classes according to PESI score. In both study phases, all the studied patients were further divided into negative (hs-cTnI-) or positive (hs-cTnI+) groups according to hs-cTnI levels within normal or above cutoff values, respectively. For all enrolled subjects, CT pulmonary angiography was analyzed to assess the RV/LV diameter and volume ratio as an indicator of RV involvement., Results: In both RS and PS phases, hs-cTnI+ group showed a higher PESI score. Nevertheless, a significant percentage of hs-cTnI+ patients resulted to be in the low-risk PESI class. Patients with a positive RV/LV ratio were more likely to have a hs-cTnI+ (p < 0.01), while among those with a negative ratio, 24 to 32% showed as hs-cTnI+. In the hs-cTnI+ group from both study phases, patients were more likely to be admitted in an ICU (RR 3.7, IC: 2.1-6.5)., Conclusions: In conclusion, in patients with PE in the ED compared PESI score alone, the combination of hs-cTnI and PESI seems to be of greater utility in improving risk stratification and final disposition decision-making.

Background and Objectives: Hemolysis is reported to be present in up to 10% of blood gas specimens in the central lab; however, few data on the incidence of hemolysis using a point-of-care testing (POCT) blood gas analysis are available in the setting of the emergency department. The aims of this study were: (1) to analyze the prevalence of hemolysis in blood gas samples collected in the ED using a POCT device; and (2) to evaluate the impact of hemolysis on blood sample results and its clinical consequences. Materials and Methods: We collected 525 consecutive POCT arterial blood gas samples using syringes with electrolyte-balanced heparin within 3 different EDs in the metropolitan area of Rome. Immediately after the collection, the blood samples were checked for the presence of hemolysis with a POCT instrument (i.e., HEMCHECK, H-10 ®). The samples were then subsequently processed for blood gasses, and an electrolytes analysis by a second operator blinded for the hemolysis results. A venous blood sample was simultaneously collected, analyzed for it’s potassium value, and used as a reference. Results: Of the samples, 472 were considered for the statistics, while 53 were excluded due to the high percentage of hemolysis due to operator fault in carrying out the measurement. The final mean hemolysis per operator was 12% (±13% SD), and the total final hemolysis was 14.4%.Potassium (K+) was significantly higher in the hemolyzed group compared with the non-hemolyzed sample (4.60 ± 0.11 vs. 3.99 ± 0.03 mEq/L; p < 0.001), and there were differences between arterial potassium versus venous potassium (D(a-v) K+, 0.29 ± 0.06 vs.−0.19 ± 0.02 mEq/L, p < 0.01). A Bland−Altman analysis confirmed that hemolysis significantly overestimated blood potassium level. Conclusion: Almost 12% of POCT blood gas analysis samples performed in the ED could be hemolyzed, and the presence of this hemolysis is not routinely detected. This could cause an error in the interpretation of the results, leading to the consideration of potassium concentrations being below the lower limit within the normal limits and also leading to the diagnosis of false hyperkalemia, which would have potential clinical consequences in therapeutic decision-making in the ED. The routine use of a POCT hemolysis detector could help prevent any misdiagnoses.

Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1-3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.

Background and Objectives: In patients with acute heart failure (AHF), there is no definite evidence on the relationship between high-sensitivity cardiac troponin (hs-cTnI) and the left ventricular ejection fraction (LVEF) comparing the reduced and preserved EF conditions. Materials and Methods: Between January and April 2022, we retrospectively analyzed the data from 386 patients admitted to the emergency departments (ED) of five hospitals in Rome, Italy, for AHF. The criteria for inclusion were a final diagnosis of AHF; a cardiac ultrasound and hs-cTnI evaluations in the ED; and age > 18 yrs. We excluded patients with acute coronary syndrome (ACS). Based on echocardiography and hs-cTnI evaluations, the patients were grouped for (1) preserved (HFpEF) or (2) reduced LVEF (HFrEF) and a a) negative (within the normal range value) or b) positive (above the normal range value) of hs-cTnI, respectively. Results: There was a significant negative relationship between a positive test for hs-cTnI and LVEF. When compared to the group with a negative hs-cTnI test, the patients with a positive test, both from the HFpEF and HFrEF subgroups, were significantly more likely to have an adverse outcome, such as being admitted to the intensive care unit (ICU) or dying in the ED. Moreover, a reduced ejection fraction was linked with a final disposition to a higher level of care. Conclusions: In patients admitted to the ED for AHF without ACS, there is a negative relationship between hs-cTnI and a reduced LVEF, although a significant percentage of patients with a preserved LVEF also resulted to have high levels of hs-cTnI. In the absence of ACS, hs-cTnI seems to be a reliable biomarker of myocardial injury in AHF in the ED and should be considered as a risk stratification parameter for these subjects regardless of the left ventricular function. Further larger prospective studies are needed to confirm these preliminary data.

Background and Objectives : In order to accelerate the risk stratification of patients referred to the Emergency Department (ED) with interstitial pneumonia, it could be useful to provide new and effective laboratory tests for use. The aim of our study was to evaluate the prognostic role of two biomarkers, bio-adrenomedullin (Bio-ADM) and proenkephalin (penKid), in patients with interstitial pneumonia (IP) at ED admission. Materials and Methods : In 153 consecutive patients with IP, both from COVID-19 or non-COVID-19 etiology, we measured, in a prospective observational manner, penKid and Bio-ADM at ED admission and after 24 h. In order to evaluate patient outcomes, 30-day follow-ups were also performed. The endpoints were 24 h, 10-day, and 30-day mortality. Results : Both biomarkers were shown to be good predictors of adverse events at 30 days, with Bio-ADM outperforming penKid. Bio-ADM was linked with 24 h and 10-day patient mortality. Moreover, PenKid was related to parameters defining worsening kidney function. Conclusions: Both in patients with COVID-19 or non-COVID-19 interstitial pneumonia at ED admission, Bio-ADM and penKid were good predictors of patient mortality. To evaluate these two biomarkers could be considered to be useful during the first evaluation in the ED when integrated with clinical scores.

Background and Objective: Sepsis is a worldwide severe disease with a high incidence and mortality rate. Sepsis is a frequent cause of admission to the emergency department (ED). Although prognostic scores (Sequential Organ Failure Assessment, SOFA; New Early Warning Score, NEWS; Rapid Emergency Medicine Score, REMS) are commonly used for risk stratification in septic patients, many of these scores are of poor utility in the ED. In this setting, biomarkers are promising alternatives, easier to perform and potentially more specific. Bio-adrenomedullin (Bio-ADM) and Proenkephalin (PenKid) seem to have a key role in the development of organ dysfunctions induced by sepsis and, therefore, could help in the risk stratification of patients with sepsis at ED admission. The aim of this study was to evaluate the utility of Bio-ADM and PenKid, obtained through a point of care (POCT) device, in predicting 30 days mortality for patients presenting to the ED with sepsis. Methods and Results: In total, 177 consecutive adult patients with a diagnosis of sepsis presenting to the ED of San Giovanni Addolorata Hospital in Rome, Italy, between May 2021 and April 2022 were enrolled in this prospective observational study. For each patient, Bio-ADM and PenKid were obtained at ED admission together with SOFA, NEWS and REMS scores. Next, 30 days follow-up data were collected to evaluate patient mortality. Both biomarkers (Bio-ADM and PenKid) and clinical scores (SOFA, NEWS and REMS) were good predictors of mortality at 30 days, with Bio-ADM and REMS outperforming the others. Moreover, PenKid resulted in being linked with the worsening of kidney function. Conclusions: In patients presenting with sepsis in the ED, Bio-ADM and PenKid, evaluated with a POCT device, predicted 30-day mortality. These two biomarkers seem even more useful when integrated with clinical risk scores at ED admission.

Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short-term unloading and active recovery (AR). Eleven healthy males underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR based on resistance exercise. Quadriceps femoris (QF) cross-sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c-terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA-sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10-day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR. KEY POINTS: We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10-day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations. After 10-day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short-term disuse at least at relatively low contraction intensities, at which low-threshold, slow-type motor units are recruited. Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage. The active recovery period restored these neuromuscular changes., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Aims and Objectives: The aim of the present paper is to provide a narrative review of the markers and pathways of periodontitis-associated insulin resistance (IR)., Materials and Methods: Research papers published in peer-reviewed scientific journals from 2000 to 2021 were searched systematically in Online Cochrane Library, Google Scholar, and MedLine/PubMed database. The medical subject headings (MeSH) terms used for literature search were "diabetes AND periodontal disease," "diabetes AND periodontitis," "inflammation AND insulin resistance," "Insulin resistance AND periodontal disease," and "insulin resistance AND periodontitis." Manual search for applicable work in review article peer-reviewed print journals, and latest editions of standard textbooks of pharmacology and pathology were searched for updated additional information. Relevant papers in English language on the topic and abstracts of pertinent articles after excluding the duplicates, animal studies, and in-vitro studies were also scrutinized thoroughly and finally included as required in this narrative review., Results: Literature search in MedLine/PubMed with MeSH words mentioned above revealed 4,621, 4,993, 19,349, 414, and 434 papers, respectively. Seven out of 13 systematic reviews and a total of 18 randomized clinical trials to evaluate periodontitis-induced IR were short-listed to update current evidences. The current literature in the past two decades has evaluated the effect of periodontal therapy on various type-2 diabetes (T2D) biomarkers following periodontal therapy. These indicators of periodontal disease activity and surrogate biomarkers of T2D in periodontitis may be an important diagnostic tool for the early prediction of complications due to IR. This increased systemic burden of proinflammatory cytokines by periodontitis can be reduced by periodontal therapy, thus improving the patient's overall systemic condition., Conclusion: The inflammatory response in periodontitis is characterized by dysregulated secretion of host-derived mediators of inflammation and tissue breakdown that may lead to IR. It can be comprehended that periodontal disease is a recognized amendable risk factor for T2D., Competing Interests: None to declare., (Copyright: © 2022 Journal of International Society of Preventive and Community Dentistry.)

Background: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined., Methods: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed., Results: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO 2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO 2 peak ≥14 ml/kg/min and SVI >30 ml/m 2 ; Group 2, score between 2 and 5 (112 patients) with VO 2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m 2 ; Group 3, score >5 (46 patients) with VO 2 peak <10 ml/kg/min and SVI <30 ml/m 2 . The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3., Conclusions: Combinations of VO 2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Given that there are no studies on diseases that occur by waiting for hospitalization, we aimed to evaluate the main causes of death in the emergency room (ER) and their relationship with overcrowding., Methods: Patients who died in the ER in the past 2 years (pediatrics and trauma victims excluded) were divided into two groups: patients who died within 6 hours of arrival (emergency department [ED] group) and patients who died later (LD group). We compared the causes of death, total vital signs, diagnostic tests performed, and therapy between the groups. We assessed for possible correlation between the number of monthly deaths per group and four variables of overcrowding: number of patients treated per month, waiting time before medical visit (W-Time), mean intervention time (I-Time), and number of patients admitted to the ward per month (NPA)., Results: During the two years, 175 patients had died in our ER (52% in ED group and 48% in LD group). The total time spent in the ER was, respectively, 2.9±0.2 hours for ED group and 17.9± 1.5 hours for LD group. The more frequent cause of death was cardiovascular syndrome (30%) in ED group and sepsis (27%) and acute respiratory failure (27%) in LD group. Positive correlations between number of monthly deaths and W-Time (R2 0.51, P<0.001), I-Time (R2 0.73, P< 0.0001), and NPA (R2 0.37, P<0.01) were found only in LD group., Conclusion: Patients with sepsis and acute respiratory failure die after a long stay in the ER, and the risk increases with overcrowding. A fast-track pathway should be considered for hospital admission of critical patients.

Accurate and temporally consistent measurements of light absorbing aerosol (LAA) heating rate (HR) and of its source apportionment (fossil-fuel, FF; biomass-burning, BB) and speciation (black and brown Carbon; BC, BrC) are needed to evaluate LAA short-term climate forcing. For this purpose, wavelength- and time-dependent accurate LAA absorption coefficients are required. HR was experimentally determined and apportioned (sources/species) in the EMEP/ACTRIS/COLOSSAL-2018 winter campaign in Milan (urban-background site). Two Aethalometers (AE31/AE33) were installed together with a MAAP, CPC, OPC, a low volume sampler (PM 2.5 ) and radiation instruments. AE31/AE33 multiple-scattering correction factors (C) were determined using two reference systems for the absorption coefficient: 1) 5-wavelength PP&#95;UniMI with low time resolution (12 h, applied to PM 2.5 samples); 2) timely-resolved MAAP data at a single wavelength. Using wavelength- and time-independent C values for the AE31 and AE33 obtained with the same reference device, the total HR showed a consistency (i.e. reproducibility) with average values comparable at 95% probability. However, if different reference devices/approaches are used, i.e. MAAP is chosen as reference instead of a PP&#95;UniMI, the HR can be overestimated by 23-30% factor (by both AE31/AE33). This became more evident focusing on HR apportionment: AE33 data (corrected by a wavelength- and time-independent C) showed higher HR FF (+24 ± 1%) and higher HR BC (+10 ± 1%) than that of AE31. Conversely, HR BB and HR BrC were -28 ± 1% and -29 ± 1% lower for AE33 compared to AE31. These inconsistencies were overcome by introducing a wavelength-dependent C λ for both AE31 and AE33, or using multi-wavelength apportionment methods, highlighting the need for further studies on the influence of wavelength corrections for HR determination. Finally, the temporally-resolved determination of C resulted in a diurnal cycle of the HR not statistically different whatever the source- speciation- apportionment used., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations., Methods: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0-5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1β and MMP-3 levels., Results: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1β and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0., Conclusions: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients.

Background and Aims: Despite the crucial role of exercise in the prevention of comorbidities and complications in type 1 diabetes mellitus (T1DM), people living with the disease are often insufficiently physically active, mainly due to the fear of hypoglycaemia. Research using continuous glucose monitoring (CGM) devices has shown that exercise affects glycaemic control in T1DM for over 24 h. The aim of this systematic review and meta-analysis is, therefore, to investigate the delayed effects of different exercise modalities on glycaemic control in adults with T1DM., Methods and Results: The literature search of experimental studies was conducted on PubMed, SPORTDiscus and EMBASE from January 2000 to September 2019. Twelve studies using CGM devices were included. Compared to endurance, intermittent exercise increased the time spent in hypoglycaemia (0.62, 0.07 to 1.18; standardised effect size, 95% CI) and reduced the mean interstitial glucose concentration (-0.88, -1.45 to -0.33). No differences emerged in the time spent in hyperglycaemia (-0.07, -0.58 to 0.45) or in the proportion of exercisers experiencing hypoglycaemic events (0.82, 0.45 to 1.49; proportion ratio, 95% CI) between conditions. The systematic review also found a reduced risk of hypoglycaemia if exercise is performed in the morning rather than in the afternoon, and with a 50% rapid-acting insulin reduction. It was not possible to determine the benefits of resistance exercise., Conclusions: For the first time, we systematically investigated the delayed effect of exercise in adults with T1DM, highlighted undetected effects, shortcomings in the existing literature, and provided suggestions to design future comparable studies., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Cancer is often accompanied by worsening of the patient's iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.

Purpose: To compare the effect of high-intensity aerobic (AER), resistance (RES), and combined (COMB: RES + AER) exercise, on interstitial glucose (IG) variability and skeletal muscle signalling pathways in type 1 diabetes (T1D)., Methods: T1D participants (6 M/6F) wore a flash glucose monitoring system in four randomized sessions: one control (CONT), and one AER, RES and COMB (40 min each). Mean amplitude of glycemic excursions (MAGE), standard deviation (SD) and coefficient variation (CV) of IG were used to compare the 24 h post-exercise IG variability. Blood and muscle samples were collected to compare exercise-induced systemic and muscle signalling responses related to metabolic, growth and inflammatory adaptations., Results: Both RES and COMB decreased the 24 h MAGE compared to CONT; additionally, COMB decreased the 24 h SD and CV. In the 6-12 h post-exercise, all exercise modalities reduced the IG CV while SD decreased only after COMB. Both AER and COMB stimulated the PGC-1α mRNA expression and promoted the splicing of IGF-1Ea variant, while Akt and p38MAPK phosphorylation increased only after RES and COMB. Additionally, COMB enhanced eEF2 activation and RES increased myogenin and MRF4 mRNA expression. Blood lactate and glycerol levels and muscle IL-6, TNF-α, and MCP-1 mRNAs increased after all exercise sessions, while serum CK and LDH level did not change., Conclusion: COMB is more effective in reducing IG fluctuations compared to single-mode AER or RES exercise. Moreover, COMB simultaneously activates muscle signalling pathways involved in substrate metabolism and anabolic adaptations, which can help to improve glycaemic control and maintain muscle health in T1D.

In this study Eucalyptus globulus essential oil was tested on major mosquito species and toxicity was compared with temephos. Mortality was calculated after 24 h and 48 h post treatment. In 24 h treatment essential oil show strong larvicidal activity with LC 50 and LC 90 values were 30.198ppm, 103.389ppm for Anopheles stephensi, 13.578ppm, 106.755ppm for Aedes aegypti ; and, 7.469ppm, 32.454ppm for Culex quinquefasciatus and 48 h post treatment LC 50 and LC 90 values were, 12.576, 49.380ppm for Anopheles stephensi, 7.926, 34.470ppm for Aedes aegypti and 4.408, 21.048ppm for Culex quinquefasciatus . Chemical composition of essential oil using GC-MS and FT-IR analysis shows the presence of 1,8-cineol, (71.7%); α-pinene, (9.14%) as a major compounds. Our findings suggest that essential oil from Eucalyptus globulus leaves can be used for control of mosquito larvae.

The use of continuous positive airway pressure (CPAP) in asthma has been a point of debate over the past several years. Various studies, including those on animals and humans have attempted to understand the role and pathophysiology of CPAP in patients with either well controlled or poorly controlled asthma. The aim of this manuscript is to review the currently available literature on the physiologic and clinical effects of CPAP in animal models of asthma and on humans with stable asthma.

Patient with idiopathic pulmonary hypertension (IPAH) develop peripheral inefficiency which could lead to an increase total energy expenditure and that could have a significant prognostic impact. To test the hypothesis, fifty-five consecutive stable IPAH patients (mean age 51±17 years) and 24 matched controls underwent an incremental exercise test and followed for a 5 years' period. Total energy expenditure was assessed as the ratio between total [Formula: see text] uptake (during both effort and recovery) and total external work ( [Formula: see text] ). Patients with IPAH had a lower exercise capacity and a significantly higher [Formula: see text] than controls ( [Formula: see text] 0.33 ± 0.09 ml/j vs 0.22 ± 0.04 ml/j, p < 0.0001). Among patients, [Formula: see text] was higher in whom died during follow up compared to survivors (0.41 ± 0.11 ml/j vs 0.30 ± 0.06 ml/j, p < 0.0001). In multivariate Cox regression analysis [Formula: see text] , gender, P ET CO 2 peak , [Formula: see text] were independent risk factors for death. Patients with IPAH have shown a less efficient muscular oxygen utilization than controls. Notably the high energy expenditure has a relevant independent prognostic impact., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The added value of cardiopulmonary exercise testing (CPET) in the follow-up of patients with stable pulmonary arterial hypertension (PAH) remains undefined., Methods: Idiopathic, heritable, and drug-induced PAH patients free from clinical worsening (CW) after 1 year of treatment were enrolled in derivation (n = 80) and validation (n = 80) cohorts at an interval of 6 years and followed for 3 years. Prognostic models were constructed and validated in low-risk patients in World Health Organization (WHO) Functional Class I or II with cardiac index (CI) ≥2.5 liters/min/m 2 and right atrial pressure (RAP) <8 mm Hg. Discrimination and calibration were assessed., Results: Forty-one derivation cohort patients had CW (51.2%) during 722 ± 349 days. Changes (∆) in WHO classification and CI and absolute value of RAP were independent predictors of CW. With addition of CPET variables, peak oxygen uptake (VO 2 peak) and ∆CI independently improved the power of the prognostic model. Receiver operating characteristic (ROC)-derived cut-off values for ∆CI and VO 2 peak were 0.40 liter/min/m 2 and 15.7 ml/kg/min (≥60% predicted value), respectively. Twenty-nine validation cohort patients had CW (36.2%) during 710 ± 282 days. Different combinations of cut-off values of VO 2 peak and ∆CI defined 4 groups. The event-free survival rates at 1, 2, and 3 years were 100%, 100%, and 100%, respectively, for the high ∆CI with high VO 2 peak combination; 100%, 88%, and 71% for low ∆CI/high VO 2 peak; 80%, 54%, and 40% for high ∆CI/low VO 2 peak; and 72%, 54%, and 33% for low ∆CI/low VO 2 peak., Conclusions: The combinations of baseline VO 2 peak and change in CI during follow-up is important in prognostication of low-risk patients with idiopathic, heritable, and drug-induced PAH., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this work PM 2.5 was collected during winter and summer in a Sardinian village (Gonnostramatza, Italy) highly affected by biomass burning emissions. A multi-technique approach was adopted for the complete PM chemical characterization. The bulk characterization was performed by IC (Ion Chromatography), HPAEC (High-Performance Anion-Exchange Chromatography), TOT (Thermal Optical Transmittance) and ED-XRF (Energy-Dispersive X-Ray Fluorescence) while XPS (X-ray Photoelectron Spectroscopy) was used for the surface characterization. Using levoglucosan as specific tracer of biomass burning emissions, the assessment of the impact of this source was carried out and it represent the major PM source at the investigate site during winter. In winter the average levoglucosan concentration is 2096 ± 324 ng/m 3 while during summer its concentration is negligible (18 ± 7 ng/m 3 ). Levoglucosan content in PM 2.5 during winter is on average 13.7%; it is estimated that 65% of PM 2.5 is due to wood burning. XPS has been exploited in this work aiming at highlighting possible differences between surface and bulk composition of PM 2.5 . The surface of the particulate matter resulted enriched in carbon compared to the bulk. Among the components of XPS C1s signals recorded on the samples collected during winter, it was found that the signal at 286.5 eV, which is due to the presence of COH, reflects the bulk composition of levoglucosan., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries.

In this paper, results from receptor modelling performed on a well-characterised PM 1 dataset were combined to chemical light extinction data (b ext ) with the aim of assessing the impact of different PM 1 components and sources on light extinction and visibility at a European polluted urban area. It is noteworthy that, at the state of the art, there are still very few papers estimating the impact of different emission sources on light extinction as we present here, although being among the major environmental challenges at many polluted areas. Following the concept of the well-known IMPROVE algorithm, here a tailored site-specific approach (recently developed by our group) was applied to assess chemical light extinction due to PM 1 components and major sources. PM 1 samples collected separately during daytime and nighttime at the urban area of Milan (Italy) were chemically characterised for elements, major ions, elemental and organic carbon, and levoglucosan. Chemical light extinction was estimated and results showed that at the investigated urban site it is heavily impacted by ammonium nitrate and organic matter. Receptor modelling (i.e. Positive Matrix Factorization, EPA-PMF 5.0) was effective to obtain source apportionment; the most reliable solution was found with 7 factors which were tentatively assigned to nitrates, sulphates, wood burning, traffic, industry, fine dust, and a Pb-rich source. The apportionment of aerosol light extinction (b ext,aer ) according to resolved sources showed that considering all samples together nitrate contributed at most (on average 41.6%), followed by sulphate, traffic, and wood burning accounting for 18.3%, 17.8% and 12.4%, respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this work, a comprehensive characterisation and source apportionment of size-segregated aerosol collected using a multistage cascade impactor was performed. The samples were collected during wintertime in Milan (Italy), which is located in the Po Valley, one of the main pollution hot-spot areas in Europe. For every sampling, size-segregated mass concentration, elemental and ionic composition, and levoglucosan concentration were determined. Size-segregated data were inverted using the program MICRON to identify and quantify modal contributions of all the measured components. The detailed chemical characterisation allowed the application of a three-way (3-D) receptor model (implemented using Multilinear Engine) for size-segregated source apportionment and chemical profiles identification. It is noteworthy that - as far as we know - this is the first time that three-way source apportionment is attempted using data of aerosol collected by traditional cascade impactors. Seven factors were identified: wood burning, industry, resuspended dust, regional aerosol, construction works, traffic 1, and traffic 2. Further insights into size-segregated factor profiles suggested that the traffic 1 factor can be associated to diesel vehicles and traffic 2 to gasoline vehicles. The regional aerosol factor resulted to be the main contributor (nearly 50%) to the droplet mode (accumulation sub-mode with modal diameter in the range 0.5-1 μm), whereas the overall contribution from the two factors related to traffic was the most important one in the other size modes (34-41%). The results showed that applying a 3-D receptor model to size-segregated samples allows identifying factors of local and regional origin while receptor modelling on integrated PM fractions usually singles out factors characterised by primary (e.g. industry, traffic, soil dust) and secondary (e.g. ammonium sulphate and nitrate) origin. Furthermore, the results suggested that the information on size-segregated chemical composition in different size classes was exploited by the model to relate primary emissions to rapidly-formed secondary compounds., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this paper, results on the potential toxicity of ultrafine particles (UFPs d<100nm) emitted by the combustion of logwood and pellet (hardwood and softwood) are reported. The data were collected during the TOBICUP (TOxicity of BIomass COmbustion generated Ultrafine Particles) project, carried out by a team composed of interdisciplinary research groups. The genotoxic evaluation was performed on A549 cells (human lung carcinomacells) using UFPs whose chemical composition was assessed by a suite of analytical techniques. Comet assay and γ-H2AX evaluation show a significant DNA damage after 24h treatment. The interpretation of the results is based on the correlation among toxicological results, chemical-physical properties of UFPs, and the type and efficiency conditions in residential pellet or logwood stoves., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Survival in patients with pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to afterload. How altered RV function impacts on exercise capacity in PAH is not exactly known.104 idiopathic PAH (IPAH) patients aged 52±14 years underwent a diagnostic right heart catheterisation, a comprehensive echocardiography including two-dimensional speckle tracking for RV dyssynchrony evaluation and a cardiopulmonary exercise test. Multivariate analyses were performed to identify independent predictors of peak oxygen uptake (peak V ' O 2 ).A first multivariate analysis of only resting haemodynamic variables identified cardiac index, right atrial (RA) pressure and pulmonary arterial compliance as independent predictors, with low predictive capacity (r 2 =0.31; p<0.001). A second multivariate analysis model which considered only echocardiographic parameters but without RV dyssynchrony, identified RV fractional area change (FAC) and RA area as independent predictors with still low predictivity (r 2 =0.35; p<0.001). Adding RV dyssynchrony to the second model increased its predictivity (r 2 =0.48; p<0.001). Repetition of the three multivariate analyses in patients with preserved RVFAC confirmed that inclusion of RV dyssynchrony results in the highest predictive capability of peak V ' O 2 (r 2 =0.53; p=0.001).A comprehensive echocardiography with speckle tracking-derived assessment of the heterogeneity of RV contraction improves the prediction of aerobic exercise capacity in IPAH., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

This work is part of the TOBICUP (TOxicity of BIomass Combustion generated Ultrafine Particles) project which aimed at providing the composition of ultrafine particles (UFPs, i.e. particles with aerodynamic diameter, d ae , lower than 100nm) emitted by wood combustion and elucidating the related toxicity. Results here reported are from two ambient monitoring campaigns carried out at an alpine town in Northern Italy, where wood burning is largely diffused for domestic heating in winter. Wintertime and summertime UFP samples were analyzed to assess their chemical composition (i.e. elements, ions, total carbon, anhydrosugars, and polycyclic aromatic hydrocarbons) and biological activity. The induction of the pro-inflammatory cytokine interleukin-8 (IL-8) by UFPs was investigated in two human cells lines (A549 and THP-1) and in human peripheral blood leukocytes. In addition, UFP-induced oxidative stress and genotoxicity were investigated in A549 cells. Ambient UFP-related effects were compared to those induced by traffic-emitted particles (DEP) taken from the NIES reference material "vehicle exhaust particulates". Ambient air UFPs induced a dose-related IL-8 release in both A549 and THP-1 cells; the effect was more relevant on summer samples and in general THP-1 cells were more sensitive than A549 cells. On a weight basis our data did not support a higher biological activity of ambient UFPs compared to DEP. The production of IL-8 in the whole blood assay indicated that UFPs reached systemic circulation and activated blood leukocytes. Comet assay and γ-H2AX evaluation showed a significant DNA damage especially in winter UFPs samples compared to control samples. Our study showed that ambient UFPs can evoke a pulmonary inflammatory response by inducing a dose-related IL-8 production and DNA damage, with different responses to UFP samples collected in the summer and winter periods., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aimed to collect, characterize ultrafine particles (UFP) generated from the combustion of wood pellets and logs (softwood and hardwood) and to evaluate their pro-inflammatory effects in THP-1 and A549 cells. Both cell lines responded to UFP producing interleukin-8 (IL-8), with wood log UFP being more active compared to pellet UFP. With the exception of higher effect observed with beech wood log UFP in THP-1, the ability of soft or hard woods to induce IL-8 release was similar. In addition, on weight mass, IL-8 release was similar or lower compared to diesel exhaust particles (DEP), arguing against higher biological activity of smaller size particles. UFP-induced IL-8 could be reduced by SB203580, indicating a role of p38MAPK activation in IL-8 production. The higher activity of beech wood log UFP in THP-1 was not due to higher uptake or endotoxin contamination. Qualitatively different protein adsorption profiles were observed, with less proteins bound to beech UFP compared to conifer UFP or DEP, which may provide higher intracellular availability of bioactive components, i.e. levoglucosan and galactosan, toward which THP-1 were more responsive compared to A549 cells. These results contribute to our understanding of particles emitted by domestic appliances and their biological effects., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

London, like many major cities, has a noted air pollution problem, and a better understanding of the sources of airborne particles in the different size fractions will facilitate the implementation and effectiveness of control strategies to reduce air pollution. Thus, the trace elemental composition of the fine and coarse fraction were analysed at hourly time resolution at urban background (North Kensington, NK) and roadside (Marylebone Road, MR) sites within central London. Unlike previous work, the current study focuses on measurements during the summer providing a snapshot of contributing sources, utilising the high time resolution to improve source identification. Roadside enrichment was observed for a large number of elements associated with traffic emissions (Al, S, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Rb and Zr), while those elements that are typically from more regional sources (e.g. Na, Cl, S and K) were not found to have an appreciable increment. Positive Matrix Factorization (PMF) was applied for the source apportionment of the particle mass at both sites with similar sources being identified, including sea salt, airborne soil, traffic emissions, secondary inorganic aerosols and a Zn-Pb source. In the fine fraction, traffic emissions was the largest contributing source at MR (31.9%), whereas it was incorporated within an "urban background" source at NK, which had contributions from wood smoke, vehicle emissions and secondary particles. Regional sources were the major contributors to the coarse fraction at both sites. Secondary inorganic aerosols (which contained influences from shipping emissions and coal combustion) source factors accounted for around 33% of the PM 10 at NK and were found to have the highest contributions from regional sources, including from the European mainland. Exhaust and non-exhaust sources both contribute appreciably to PM 10 levels at the MR site, highlighting the continuing importance of vehicle-related air pollutants at roadside., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension. The aim of the study was to evaluate the incremental prognostic value of echocardiography of the right ventricle and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients., Methods: One hundred and thirty treatment-naïve patients with idiopathic pulmonary arterial hypertension were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-min walk distance plus an increase in functional class, or nonelective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic, and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done., Results: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical, and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (model 1). With addition of echocardiographic and CPET variables (model 2), peak O 2 pulse (peak V˙o 2 /heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (area under the curve, 0.81 vs 0.66, respectively; P = .005). Patients with low RVFAC and low O 2 pulse (low RVFAC + low O 2 pulse) and high RVFAC + low O 2 pulse showed a 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk, 41.1 and 25.3, respectively), compared with high RVFAC + high O 2 pulse (P = .0001)., Conclusions: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O 2 pulse identifies patients at a particularly high risk of clinical deterioration., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Advanced receptor models have been recently developed and tested in order to improve the resolution of apportionment problems reducing rotational ambiguity of results and aiming at identifying a larger number of sources. In particular, multi-time model is a factor analysis method able to compute source profiles and contributions using aerosol compositional data with different time resolutions. Unlike traditional factor analysis, each measured value can be inserted into multi-time model with its original time schedule, thus all temporal information can be effectively used in the modelling process. In this work, multi-time model was expanded in order to impose constraints on modelled factors aiming at improving the source identification. Moreover, as far as we know for the first time, a suitable bootstrap technique was implemented in the multi-time scheme to estimate the uncertainty of the final constrained solutions. These implemented approaches were tested on a PM2.5 (particulate matter with aerodynamic diameter <2.5 μm) dataset composed of 24-h samples collected during one year and hourly data sampled in parallel for two shorter periods in Florence (Italy). The daily samples were chemically characterised for elements, ions and carbonaceous components while elemental concentrations only were available for high-time resolved samples. The application of the advanced model revealed the major contribution from traffic (accounting for 37% of PM2.5 as annual average) and allowed an accurate characterisation of involved emission processes. In particular, exhaust and non-exhaust emissions were identified. The constraints imposed in the continuation run led to a better description of the factor associated to nitrates and also of biomass burning profile and the bootstrap results gave useful information to assess the reliability of source apportionment solutions. Finally, the comparison with the results computed by ME-2 base model applied to daily and hourly compositional data separately demonstrated the advantages provided by the multi-time approach., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension., Background: Right ventricular dyssynchrony has been described in pulmonary arterial hypertension, but no evidence is available on its prognostic impact and evolution after therapy., Methods: In 83 consecutive therapy-naïve patients, right ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking echocardiography calculating the standard deviation of the times to peak-systolic strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test [6 MWT]), a second assessment was performed after 12 months or when clinical worsening occurred., Results: Patients with right ventricular dyssynchrony (RV-SD4 >18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and hemodynamic profile compared with patients ≤ 18 ms. Determinants of dyssynchrony included pulmonary vascular resistance, QRS duration, and right ventricular end-diastolic area (r(2) = 0.38; p < 0.000001). At 12 months, 32.5% of patients presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year). Multivariable models for clinical worsening prediction showed that the addition of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac index) significantly increased the prognostic power of the model (0.74 vs. 0.81; p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating characteristic analysis identified RV-SD4 ≥ 23 ms as the best cutoff value for clinical worsening prediction (95% negative predictive value). At 12 months, normalization of dyssynchrony was achieved in patients with a large reduction of pulmonary vascular resistance (-42 ± 4%)., Conclusions: Right ventricular dyssynchrony is frequent in pulmonary arterial hypertension, is an independent predictor of clinical worsening, and might regress during effective treatments., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In 2011 the European Society of Cardiology published the new guidelines for the treatment and management of acute coronary syndrome without elevation of the ST segment (NSTEMI). For the treatment of the syndrome, the use of P2Y12 inhibitors in addition to aspirin was strongly recommended (evidence IA). We studied the application of this recommendation in the setting of the emergency department in the vast and uneven area of the Italian region Lazio, three years after the release of these drugs in Italy., Methods: 121 consecutive patients (65% older than 65 years) affected by NSTEMI were recruited between May and July 2013. During the transition in the emergency department data was collected on patient's symptoms, syndrome severity and type & timing of treatments chosen. Adherence to the guidelines was evaluated considering the number of "good treated" patients: these being the patients that received at least 80% of the main five recommendations on percutaneous coronary intervention (PCI) timing, antiplatelet and anti-coagulant therapy suggested by the European Cardiology Task Force (ESC guidelines, 2011) for the very acute phase of NSTEMI., Results: Patients were treated with: 1) 35% of cases with double antiplatelet therapy and anticoagulation (DAPT+AC), 2) 22% of cases with single antiplatelet and anticoagulation (SAPT+AC), 3) 6% of cases with a single antiplatelet therapy (SAPT), 4) 6% of cases with a double antiplatelet therapy (DAPT) and 5) 24% of cases did not receive any therapy. Data on PCI was available for 95 patients and, of these, only 82% of the patients underwent the procedure. The percentage of "good treated" patients were among of 20-40%, depending on PCI timing--as guidelines suggested--was considered as mandatory (20,5%) or as the extreme time limit (40%). Significant differences were found between patients treated in a central hospital with a hemodynamic laboratory active 24/24hr (HUB) and patients treated in the other hospital (SPOKE). HUBs showed a higher percent of "good treated" patients, a higher percentage of early invasive treated and a better adherence to recommended pharmacological therapy., Conclusions: A significant number of patients did not receive adequate treatment during the emergency department stay. The absence of hemodynamic services increases the risk of inadequate treatment.

In this study, the Multilinear Engine (ME-2) receptor model was applied to speciated particulate matter concentration data collected with two different measuring instruments upwind and downwind of a steelworks complex in Port Talbot, South Wales, United Kingdom. Hourly and daily PM samples were collected with Streaker and Partisol samplers, respectively, during a one month sampling campaign between April 18 and May 16, 2012. Daily samples (PM10, PM2.5, PM2.5-10) were analysed for trace metals and water-soluble ions using standard procedures. Hourly samples (PM2.5 and PM2.5-10) were assayed for 22 elements by Particle Induced X-ray Emission (PIXE). PM10 data analysis using ME-2 resolved 6 factors from both datasets identifying different steel processing units including emissions from the blast furnaces (BF), the basic oxygen furnace steelmaking plant (BOS), the coke-making plant, and the sinter plant. Steelworks emissions were the main contributors to PM10 accounting for 45% of the mass when including also secondary aerosol. The blast furnaces were the largest emitter of primary PM10 in the study area, explaining about one-fifth of the mass. Other source contributions to PM10 were from marine aerosol (28%), traffic (16%), and background aerosol (11%). ME-2 analysis was also performed on daily PM2.5 and PM2.5-10 data resolving 7 and 6 factors, respectively. The largest contributions to PM2.5-10 were from marine aerosol (30%) and blast furnace emissions (28%). Secondary components explained one-half of PM2.5 mass. The influence of steelworks sources on ambient particulate matter at Port Talbot was distinguishable for several separate processing sections within the steelworks in all PM fractions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Context: High altitude (HA) is a model of severe hypoxia exposure in humans. We hypothesized that nocturnal hypoxemia or acute maximal exercise at HA might affect plasma leptin and VEGF levels., Objectives: Plasma leptin, VEGF and other metabolic variables were studied after nocturnal pulse oximetry and after maximal exercise in healthy lowlanders on the 3rd-4th day of stay in Lobuche (5050 m, HA) and after return to sea level (SL)., Results: Leptin was similar at SL or HA in both pre- and post-exercise conditions. Pre-exercise VEGF at HA was lower, and cortisol was higher, than at SL, suggesting that nocturnal intermittent hypoxia associated with periodic breathing at HA might affect these variables., Conclusions: Leptin levels appear unaffected at HA, whereas nocturnal hypoxic stress may affect plasma VEGF. Future HA studies should investigate the possible role of nocturnal intermittent hypoxemia on metabolism.

irth weight is an important determinant of child survival, healthy growth and development. Low birth weight is a well-established risk factor for adverse long term health, particularly cardiovascular disease and metabolic syndrome. The ability of the fetus to grow and thrive in utero is presumed to be a function of the placenta. The present study was aimed to assess the morphometry examination of placenta in normal and low birth weight babies in the Union territory of Puducherry. Morphometry examination includes Placenta weight, number of cotyledons, maternal and fetal surface area and site of umbilical cord insertion were measured in normal and low birth weigh babies. Result showed among 200 subjects, mean birth weight of normal and low birth babies were 2806 and 2058 g, respectively. The prevalence rate of low birth babies (less than 2500 g) was 22%. The placental morphometry study namely placental weight, number of cotyledons, maternal and fetal surface area and insertion of umbilical cord at centre were significantly (p<0.001) reduced in the low birth weight babies when compared with normal birth weight babies. Study revealed that morphometry analysis of placenta significantly influences the birth weight of new born. In conclusion, study recommends the early measurements of placenta by non-invasive techniques like ultrasonography will be helpful in early prediction of low birth weight fetus in utero itself and for better management to avoid such low birth weight.

Background: The ventilatory compensation point (VCP) is an exercise threshold which has been used in the design of training programs in sports medicine and rehabilitation. We recently demonstrated that changes in the slope of the minute ventilation to heart rate relationship (ΔV˙E/ΔHR) can be utilized for estimation of the VCP during incremental exercise at sea level (SL). We hypothesized that in hypoxic conditions, such as high altitude (HA), VCP can be also reliably estimated by ΔV˙E/ΔHR., Methods: At SL and on immediate ascent to HA (5,050 m), six healthy subjects (42 ± 14 SD years) performed a maximal incremental exercise test on a cycle ergometer; O2 uptake (V˙O2), CO2 output (V˙CO2), V˙E, and HR were measured breath-by-breath. The ΔV˙E/ΔHR method for VCP estimation was compared to the standard method using the ventilatory equivalent for CO2 (V˙E/V˙CO2) and end-tidal PCO2 (PETCO2). The ΔV˙E/ΔHR slope values below (S1) and above (S2) VCP were computed by linear regression analysis., Results: A significant difference between S1 and S2 was observed, at SL and HA, for both the ΔV˙E/ΔHR and V˙E/V˙CO2 methods for VCP estimation. A good agreement between the two methods (ΔV˙E/ΔHR vs. V˙E/V˙CO2) was found for both environmental conditions; the mean difference ± 2 SD of V˙O2 at VCP (VCP-V˙O2) was -22 ± 112 ml/min at SL and 39 ± 81 ml/min at HA. The VCP-V˙O2 was significantly lower at HA compared to SL; in addition, S1 and S2 mean values were significantly higher at HA compared to SL., Conclusion: At HA, VCP may be reliably estimated by the ΔV˙E/ΔHR method.