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Critical illness myopathy (CIM) detrimentally affects muscle function in ICU patients, with a dramatic loss of muscle mass and function where the loss in specific force exceeds the loss in muscle mass (maximum force normalized to muscle cross-sectional area). The preferential loss of the molecular motor protein myosin, representing the hallmark of CIM, exhibiting a significant negative impact on the specific force generation by the muscle. Interestingly however, the preferential myosin loss is a relatively late event, and a specific loss in force generation capacity, is observed prior to the myosin loss. In the current study, employing an optimized cadmium telluride quantum dots (QD) mediated-thermometry approach to assess the efficiency of the myosin, we were able to determine the loss in specific force generated by the muscle, prior to the preferential loss of myosin. Reduction in QD fluorescent intensity correlates with greater heat loss, reflecting inefficient myosin function (less mechanical work performed and more heat loss on ATP hydrolysis by myosin). A significant decrease in myosin efficiency was observed in rats subjected to the ICU condition (immobilization and mechanical ventilation) for 5 days using an established experimental ICU model not limited by early mortality. Thus, qualitative myosin changes preceding quantitative myosin loss offer a mechanism underlying the early loss in specific force generation capacity associated with CIM and opens a venue for future CIM intervention strategies. [ABSTRACT FROM AUTHOR]

This letter, published in the American Journal of Respiratory Cell & Molecular Biology, discusses the need for early diagnosis and intervention to reduce the negative effects of ventilator-induced lung injury (VILI). The authors conducted a time-course proteomic study using a unique experimental ICU model and observed significant alterations in the proteomic profiles of bronchoalveolar lavage fluid (BALF) from Day 5 to Day 8 of mechanical ventilation (MV), indicating VILI. They identified potential biomarkers for VILI, such as MMP9 and intracellular proteins originating from lung and bronchial epithelial cells. The study highlights the importance of biomarkers for early detection of VILI to improve patient outcomes. [Extracted from the article]

Aim: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator‐induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. Methods: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. Results: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two‐fold P‐STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post‐translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P‐STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. Conclusion: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator‐induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD. [ABSTRACT FROM AUTHOR]

The ammonia spectrum is revisited in the important 1.6 µm atmospheric transparency window between 5650 and 6350 cm $ ^{-1} $ − 1 on the basis of recently recorded high-resolution Fourier transform spectra. These spectra offer an improved frequency sampling and better traceability of the measurement conditions compared to previously studied Kitt Peak spectra (Cacciani et al. J. Quant Spectrosc Radiat Transf 2021; 258:107334. https://doi.org/10.1016/j.jqsrt.2020.107334). Overall, 4812 $ ^{14} $ 14 NH $ _3 $ 3 lines were measured in the 5650–6350 cm $ ^{-1} $ − 1 region corresponding to 4866 transitions including 2066 new ones compared with our previous study, included in the HITRAN2020 database. The energy of 1023 upper state levels (including 107 new ones) was derived from 2608 assigned transitions. Independently, ammonia spectra recorded in a supersonic jet expansion using a tunable extended cavity diode laser allow us to check the absolute transition energies in the 5980–6080 cm $ ^{-1} $ − 1 range. Accurate jet spectra calibration was achieved using CH $ _4 $ 4 reference line positions known with kHz accuracy. The position agreement with the FTS data is within the $ 4\times 10^{-4} $ 4 × 10 − 4 cm $ ^{-1} $ − 1 uncertainty of the positions measured in the jet expansion. A recommended line list of 5620 transitions is provided for $ ^{14} $ 14 NH $ _3 $ 3 in the considered 5650–6350 cm $ ^{-1} $ − 1 region. [ABSTRACT FROM AUTHOR]

Migrants may be susceptible to vaccine barriers and hesitancy. We evaluated the association between migrant status, as measured by the citizenship from a High Migratory Pressure Country (HMPC), and COVID-19 vaccination uptake in the resident population in Rome, Italy. We also investigated sex differences. We followed participants for vaccination against COVID-19 in 2021. We calculated crude- and adjusted-vaccination rates and Cox hazard ratios of vaccination for migrants compared to Italians. Among migrants from HMPCs, we estimated HRs for females compared to males, stratifying by geographical area of origin. Models were adjusted for age and deprivation index and stratified by infection history. In 2021, among 1,731,832 18–64-year-olds, migrants were 55% less likely to uptake at least one COVID-19 vaccine dose than their Italian counterpart. Past SARS-CoV-2 infection reduced the difference between migrants and Italians to 27%. Among migrants from HMPCs, we observed a slight excess of vaccination uptake among females compared to males. Focusing on geographical areas, we observed that only females from central-western Asia were 9% less likely to uptake vaccination than males. Health communication strategies oriented to migrants and considering their different languages, cultures, and health literacy should be adopted for prevention before emergencies. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. Methods: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. Results: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. Conclusions: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients. [ABSTRACT FROM AUTHOR]

Ventilator-induced diaphragm dysfunction (VIDD) is a common sequela of intensive care unit (ICU) treatment requiring mechanical ventilation (MV) and neuromuscular blockade (NMBA). It is characterised by diaphragm weakness, prolonged respirator weaning and adverse outcomes. Dissociative glucocorticoids (e.g., vamorolone, VBP-15) and chaperone co-inducers (e.g., BGP-15) previously showed positive effects in an ICU-rat model. In limb muscle critical illness myopathy, preferential myosin loss prevails, while myofibrillar protein post-translational modifications are more dominant in VIDD. It is not known whether the marked decline in specific force (force normalised to cross-sectional area) is a pure consequence of altered contractility signaling or whether diaphragm weakness also has a structural correlate through sterical remodeling of myofibrillar cytoarchitecture, how quickly it develops, and to which extent VBP-15 or BGP-15 may specifically recover myofibrillar geometry. To address these questions, we performed label-free multiphoton Second Harmonic Generation (SHG) imaging followed by quantitative morphometry in single diaphragm muscle fibres from healthy rats subjected to five or 10 days of MV + NMBA to simulate ICU treatment without underlying confounding pathology (like sepsis). Rats received daily treatment of either Prednisolone, VBP-15, BGP-15 or none. Myosin-II SHG signal intensities, fibre diameters (FD) as well as the parameters of myofibrillar angular parallelism (cosine angle sum, CAS) and in-register of adjacent myofibrils (Vernier density, VD) were computed from SHG images. ICU treatment caused a decline in FD at day 10 as well as a significant decline in CAS and VD from day 5. Vamorolone effectively recovered FD at day 10, while BGP-15 was more effective at day 5. BGP-15 was more effective than VBP-15 in recovering CAS at day 10 although not to control levels. In-register VD levels were restored at day 10 by both compounds. Our study is the first to provide quantitative insights into VIDD-related myofibrillar remodeling unravelled by SHG imaging, suggesting that both VBP-15 and BGP-15 can effectively ameliorate the structure-related dysfunction in VIDD. [ABSTRACT FROM AUTHOR]

The Weather Research and Forecast (WRF) model is used to simulate atmospheric circulation during the summer season in a coastal region of central Italy, including the city of Rome. The time series of surface air temperature, wind speed, and direction are compared with in situ observations in urban Rome and its rural surroundings. Moreover, the vertical wind profiles are compared to sodar urban measurements. To improve the WRF model's ability to reproduce the local circulation, and the onset and propagation of the sea breeze, several simulations are carried out modifying the land use and the thermal and physical properties of the surfaces. Based on the results of the correlation coefficient and the RMSE, the heat capacity and albedo are the parameters mostly influencing the daily temperature cycle. Particularly, the temperature in the urban area is reproduced more realistically when the heat capacity is increased. Hence, the best simulations are used to initialize a large-eddy simulation at high spatial resolution to analyze the interaction between the sea breeze and the urban heat island and to investigate the interaction of the sea breeze front with orography and surface roughness. As confirmed by observations collected by in situ weather stations in the surroundings of Rome, the front, entering the city, splits into three branches: (i) a west component in the western flank of the city, closer to the sea; (ii) a north-west component in the northern, inland side, and (iii) a south-west component in the south area of the city. [ABSTRACT FROM AUTHOR]

This study presents a trend analysis of a two-decade (2000–2020) series of surface meteorological and air quality data measured in Rome (Italy). Data series are collected at three sites in Rome downtown and its coastal surroundings. This paper fills the gap due to missing or incomplete recent information about the meteorological and atmospheric composition tendencies in the Rome area. Datasets are subjected to in-depth quality control and to statistical analysis to verify the data homogeneity, whilst trend analysis is performed using the Seasonal Kendall test. The results show a statistically significant positive trend for average air temperature (0.07 °C year−1 in urban and coastal sites), whilst maximum and minimum temperatures increase more in urban (0.10 °C year−1) than in coastal (0.01 °C year−1) environment. The water vapour mixing ratio trend is higher in the city (0.10 g kg−1 year−1) than along the coast (0.03 g kg−1 year−1). The heat index tendency is more pronounced in the Rome centre (0.11 °C year−1) than in the coast (0.06 °C year−1). The monthly cumulative precipitations do not show statistically significant trends. On the other hand, air quality generally improved: surface pollutant concentrations show a significant decrease thanks to the reduction of local emissions (C6H6, − 0.12 µg m−3 year−1; SO2, − 0.09 µg m−3 year−1; CO, − 0.02 mg m−3 year−1; NOx, − 1.28 µg m−3 year−1; NO, − 0.38 µg m−3 year−1; NO2, − 0.60 µg m−3 year−1, PM10, − 0.35 µg m−3 year−1). Only O3 shows a statistically significant positive trend (0.15 µg m−3 year−1), in agreement with wider scale studies. The outcomes suggest that whilst local and national policies contribute to the improvement of air quality, the rising of temperature—as likely consequence of climate change—may be an emerging cause of concern for human thermal discomfort and potential effect on the conservation of tangible immovable heritage. [ABSTRACT FROM AUTHOR]

Prolonged mechanical ventilation for critically ill patients with respiratory distress can result in severe muscle wasting with preferential loss of myosin. Systemic inflammation triggered by lung mechanical injury likely contributes to this myopathy, although the exact mechanisms are unknown. In this study, we hypothesized that muscle wasting following mechanical ventilation is accompanied by bone loss. The objective was to determine the rate, nature, and extent of bone loss in the femora of rats ventilated up to 10 days and to relate the bone changes to muscle deterioration. We have developed a rat model of ventilator‐induced muscle wasting and established its feasibility and clinical validity. This model involves pharmacologic paralysis, parenteral nutrition, and continuous mechanical ventilation. We assessed the hindlimb muscle and bone of rats ventilated for 0, 2, 5, 8, and 10 days. Routine histology, microCT, and biomechanical evaluations were performed. Hindlimb muscles developed changes consistent with myopathy, whereas the femurs demonstrated a progressive decline in trabecular bone volume, mineral density, and microarchitecture beginning Day 8 of mechanical ventilation. Biomechanical testing showed a reduction in flexural strength and stiffness on Day 10. The bone changes correlated with the loss of muscle mass and myosin. These results demonstrate that mechanical ventilation leads to progressive trabecular bone loss parallel to muscle deterioration. The results of our study suggest that mechanically ventilated patients may be at risk of compromised bone integrity and muscle weakness, predisposing to post‐ventilator falls and fractures, thereby warranting interventions to prevent progressive bone and muscle decline. [ABSTRACT FROM AUTHOR]

The impact of the aerosol optical properties on the ultraviolet index (UVI) in the urban area of Rome is investigated in this study. In particular, the influence of aerosol optical depth (AOD) and single scattering albedo (SSA), estimated at the wavelength of 340 nm, and of the Ångström exponent, calculated in the range 340–500 nm, over a period of 11 years (2010–2020) in the months from March to September are analyzed. The UVI is monitored by a Brewer spectrophotometer, whereas measurements of the direct Sun and diffuse sky irradiances are performed by a co-located PREDE-POM sun–sky radiometer of the ESR/SKYNET network; the aerosol optical properties are obtained by the Skyrad MRIv2 retrieval. A novel method, based on physical principles and easily adaptable to other contexts, is developed to extrapolate the aerosol properties to the UV range during periods when only visible to near-infrared measurements are available. The retrievals from the sun–sky radiometer are consistent with the chemical characterization of urban PM 10 (particulate matter 10 mm or less in diameter) samples collected during an intensive field campaign held in summer 2011 at the same site (URBan Sustainability Related to Observed and Monitored Aerosol – URBS ROMA). The PM macro components identified during the campaign are grouped in order to evaluate the contribution of the main macro sources (soil, sea, secondary inorganic, organics, and traffic) whose relative role is indeed expected to strongly affect the aerosol absorption capability. The surface forcing efficiency, calculated as the change in the UV index for a unit AOD variation, shows that AOD is the primary parameter affecting the surface irradiance under clear-sky conditions in Rome. SSA and the Ångström exponent are also identified as secondary influencing factors, i.e., the surface forcing efficiency is found to be greater for smaller zenith angles and for larger and more absorbent particles in the UV range (such as, e.g., mineral dust). [ABSTRACT FROM AUTHOR]

In coastal regions, the complex interaction of synoptic-scale dynamics and breeze regimes influence the local atmospheric circulation, permitting to distinguish typical yet alternative patterns. In this paper, the k-means clustering algorithm is applied to the hourly time series of wind intensity and direction collected by in-situ weather stations at seven locations within 30 km from the western coastline of central Italy, in the proximity of Rome, over the period 2014–2020. The selection of both wind-integral quantities and ad hoc objective parameters allows for the identification of three characteristic clusters, two of which are closely related to the synoptic circulation and governed by persistent winds, blowing from either the northeast or the southeast direction throughout the day. In the latter case, synoptic and mesoscale contributions add up, giving rise to a complex circulation at the ground level. On the contrary, the third cluster is closely related to the sea breeze regime. The results allow the identification of some general information about the low-level circulation, showing that the synoptic circulation dominates in winter and, partly, in spring and autumn, when high ventilation and low recirculation conditions occur. Conversely, during summer the sea breeze regime is more frequent and stronger, generating intense air recirculation. Our analysis permits to discern rigorously and objectively the typical coastal meteorological patterns, only requiring anemological in-situ data. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders (ASD) symptoms and internalized stigma (or self-stigma) can have a negative impact on cognitive and functional outcomes in people living with schizophrenia. Aim of the present study were to assess and compare internalized stigma, subjective well-being and other socio-demographic, clinical and functional characteristics in people diagnosed with schizophrenia with and without prominent autistic features. Ninety-four inpatients were assessed with measures of internalized stigma, subjective well-being, global clinical severity, schizophrenia symptoms severity, real-world functioning, medication side effects and attitude toward prescribed medications. Subjects with high levels of ASD symptoms were identified with the PANSS Autism Severity Score and compared to other participants. Predictors of prominent ASD features were also assessed. Thirteen patients showed prominent ASD symptoms. They were characterized by fewer years of education, worse real-world functioning and greater symptoms severity. No between-group differences were observed regarding subjective well-being and global internalized stigma severity; however, participants in the "autistic schizophrenia" group showed better stigma resistance. A worse clinical condition and fewer years of education emerged as predictors of autistic schizophrenia. Despite showing a more severe clinical presentation of the disorder and worse functional impairment, participants with prominent ASD symptoms do not present worse subjective well-being or more severe internalized stigma; on the contrary, they show better stigma resistance. ASD symptoms could therefore play a protective role in the internalization of stigma. [ABSTRACT FROM AUTHOR]

The Boundary layer Air Quality-analysis Using Network of Instruments (BAQUNIN) supersite is presented. The site has been collecting pollutant concentrations and meteorological parameters since 2017. Currently, BAQUNIN consists of three observation sites located in the city center of Rome (Italy), and in the neighboring semirural and rural areas. To the best of our knowledge, BAQUNIN is one of the first observatories in the world to involve several passive and active ground-based instruments installed in multiple locations, managed by different research institutions, in a highly polluted megacity affected by coastal weather regimes. BAQUNIN has been promoted by the European Space Agency to establish an experimental research infrastructure for the validation of present and future satellite atmospheric products and the in-depth investigation of the planetary and urban boundary layers. Here, the main characteristics of the three sites are described, providing information about the complex instrumental suite and the produced data. The supersite adopts a policy of free sharing of its validated dataset with the community. Finally, the BAQUNIN potential is demonstrated with a case study involving a major fire that occurred in a waste treatment plant near the urban center of Rome, and the consequent investigation of the plume properties revealed by different instruments. [ABSTRACT FROM AUTHOR]

Background: In Europe, one of the most consistent findings is that of migrant mortality advantage in high-income countries. Furthermore, the literature shows that economic shocks, which bring worse health outcomes, can severely affect the most disadvantaged individuals. We analyse differences and changes in all-cause mortality between Italians and migrants residing in Rome before, during, and in the aftermath of the Great Recession (2001-2015) by birth-cohort.Methods: The analysis is a longitudinal open cohort study. Mortality data come from the Register of the Causes of Death (58,637 deaths) and the population denominator (n = 2,454,410) comes from the Municipal Register of Rome. By comparing three time-periods (2001-2005, 2006-2010, and 2011-2015), we analyse all-cause mortality of Rome residents born, respectively, in the intervals 1937-1976, 1942-1981, 1947-1986 (aged 25-64 years at entry into observation). Computing birth-cohort-specific death rates and applying parametric survival models with age as the time-scale, we compare mortality differences between migrants and Italians by gender, area of origin, and time-period.Results: Overall, we find a lower risk of dying for migrants than Italians regardless of gender (Women: HR = 0.61, 95% CI 0.56-0.66; Men: HR = 0.49, 95% CI 0.45-0.53), and a lower death risk over time for the total population. Nevertheless, such a pattern changes according to gender and migrants' area of origin.Conclusion: Given the relevance of international migrations in Europe, studying migrants' health has proved increasingly important. The deterioration in migrant health and the gradual weakening of migrants' mortality advantage is likely to become a public health issue with important consequences for the healthcare system of all European countries. [ABSTRACT FROM AUTHOR]

Purpose: Pituitary metastases (PM) are uncommon findings and are mainly derived from breast and lung cancers. No extensive review of PM from neuroendocrine neoplasms (NENs) is on record. Here we describe a clinical case of PM from pancreatic NEN and review the clinical features of PM from NENs reported in the literature. Methods: A case of PM from a pancreatic NEN followed at our institution is described. We also reviewed the 43 cases of PM from NENs reported in the literature. Results: A 59-year old female patient, previously submitted to duodeno-cephalo-pancreasectomy for a well-differentiated pancreatic NEN, with known hepatic metastases, underwent a 68 Ga-DOTATOC PET/CT that revealed an uptake in the pituitary gland. A subsequent MRI displayed a pituitary lesion, with suprasellar extension. After a hormonal and genetic diagnostic workup that excluded the diagnosis of MEN 1, the worsening of headache and visual impairment and the growth of the lesion lead to its surgical removal. A pituitary localization of the pancreatic NEN was identified. Regarding the published cases of PM from NENs, the most common tumour type was small cell lung cancer (SCLC), accounting for nearly half of the cases, followed by bronchial and pancreatic well differentiated NENs. The most frequent symptom was a variable degree of visual impairment, while headache was reported in half of the cases. Partial or total anterior hypopituitarism was present in approximately three quarters of the cases, while diabetes insipidus was less common. The most frequent treatment for PM was surgical resection, followed by radiotherapy and chemotherapy. The clinical outcome was in line with previous reports of PM from solid tumours, with a median survival of 14 months. Surgery of PM was associated with prolonged survival. Conclusions: PM from NENs have clinical features similar to metastases derived from other solid tumours, albeit the involvement of the anterior pituitary seems more frequent; a thorough pituitary hormonal evaluation is mandatory, after focused radiological studies, particularly if a surgical approach is considered. The optimal management of PM remains disputed and seems mainly driven by the aggressiveness of the primary tumour and the presence of symptoms. In well-differentiated NENs, particularly in the case of symptomatic PM, surgical removal may be a reasonable approach. [ABSTRACT FROM AUTHOR]

Key points: Critical illness myopathy (CIM) is a frequently observed negative consequence of modern critical care.Chronic Janus kinase (JAK)/signal transducer and activator of transcription activation impairs muscle size and function and is prominent following mechanical ventilation.We identify pSTAT‐3 activation in tibialis anterior of CIM patients, before examining the potential benefits of JAK1/2 inhibition in an experimental model of CIM, where muscle mass and function are impaired.CIM activates complement cascade and increased monocyte infiltration in the soleus muscle, which was ameliorated by JAK1/2 inhibition, leading to reduced muscle degeneration and improved muscle force.Here, we demonstrate that JAK1/2 inhibition augments CIM muscle function through regulation of the complement cascade. Critical illness myopathy (CIM) is frequently observed in response to modern critical care with negative consequences for patient quality of life, morbidity, mortality and healthcare costs. Janus kinase (JAK)/signal transducer and activator of transcription (STAT) activation is observed in limb muscles following controlled mechanical ventilation. Chronic JAK/STAT activation promotes loss of muscle mass and function. Thus, we hypothesized that JAK1/2 inhibition would improve muscle outcomes for CIM. Following 12 days of intensive care unit conditions, pSTAT‐3 levels increased in tibialis anterior muscle of CIM patients (P = 0.0489). The potential of JAK1/2 inhibition was assessed in an experimental model of CIM, where soleus muscle size and force are impaired. JAK1/2 inhibition restores soleus force (P < 0.0001). CIM activated muscle complement cascade, which was ameliorated by JAK1/2 inhibition (P < 0.05, respectively). Soleus macrophage number corresponded with complement activity, leading to reduced muscle degeneration and augmented muscle function (P < 0.05). Thus, JAK/STAT inhibition improves soleus function by modulating the complement cascade and muscle monocyte infiltration. Collectively, we demonstrate that JAK/STAT inhibition augments muscle function in CIM. Key points: Critical illness myopathy (CIM) is a frequently observed negative consequence of modern critical care.Chronic Janus kinase (JAK)/signal transducer and activator of transcription activation impairs muscle size and function and is prominent following mechanical ventilation.We identify pSTAT‐3 activation in tibialis anterior of CIM patients, before examining the potential benefits of JAK1/2 inhibition in an experimental model of CIM, where muscle mass and function are impaired.CIM activates complement cascade and increased monocyte infiltration in the soleus muscle, which was ameliorated by JAK1/2 inhibition, leading to reduced muscle degeneration and improved muscle force.Here, we demonstrate that JAK1/2 inhibition augments CIM muscle function through regulation of the complement cascade. [ABSTRACT FROM AUTHOR]

Background: Old age is associated with a significantly increased mortality in COVID-19 patients exposed to long-term controlled mechanical ventilation (CMV) and suggested to be due to the hyperinflammatory response associated with the viral infection. However, our understanding of age-related differences in the response to CMV in the absence of a viral infection remains insufficient. Methods: Young (7–8 months) and old (28–32 months) F344 BN hybrid rats were exposed to the ICU condition for 5 days, i.e., complete immobilization, mechanical ventilation, and extensive monitoring. Transcriptomic (RNA-Seq) and proteomics (Proximity Extension Assay) analyses of the diaphragm and proteomics analysis of plasma were conducted to investigate the molecular differences between young and old rats exposed to the ICU condition. Results: According to multi-omics analyses, significant differences were observed in the diaphragm between young and old rats in response to 5 days CMV and immobilization. In young rats, metabolic pathways were primarily downregulated in response to immobilization (post-synaptic blockade of neuromuscular transmission). In old rats, on the other hand, dramatic immune and inflammatory responses were observed, i.e., an upregulation of specific related pathways such as "IL-17 signaling pathway", along with a higher level of inflammatory factors and cytokine/chemokine in plasma. Conclusions: The dramatically increased mortality in old ICU patients with COVID-19-associated hyperinflammation and cytokine storm need not only reflect the viral infection but may also be associated with the ventilator induced diaphragm dysfunction (VIDD) and hyperinflammatory responses induced by long-term CMV per se. Although mechanical ventilation is a life-saving intervention in COVID-19 ICU patients, CMV should be cautiously used especially in old age and other means of respiratory support may be considered, such as negative pressure ventilation. [ABSTRACT FROM AUTHOR]

Background: Nanotoxicology is an increasingly relevant field and sound paradigms on how inhaled nanoparticles (NPs) interact with organs at the cellular level, causing harmful conditions, have yet to be established. This is particularly true in the case of the cardiovascular system, where experimental and clinical evidence shows morphological and functional damage associated with NP exposure. Giving the increasing interest on cobalt oxide (Co3O4) NPs applications in industrial and bio-medical fields, a detailed knowledge of the involved toxicological effects is required, in view of assessing health risk for subjects/workers daily exposed to nanomaterials. Specifically, it is of interest to evaluate whether NPs enter cardiac cells and interact with cell function. We addressed this issue by investigating the effect of acute exposure to Co3O4-NPs on excitation-contraction coupling in freshly isolated rat ventricular myocytes. Results: Patch clamp analysis showed instability of resting membrane potential, decrease in membrane electrical capacitance, and dose-dependent decrease in action potential duration in cardiomyocytes acutely exposed to Co3O4-NPs. Motion detection and intracellular calcium fluorescence highlighted a parallel impairment of cell contractility in comparison with controls. Specifically, NP-treated cardiomyocytes exhibited a dose-dependent decrease in the fraction of shortening and in the maximal rate of shortening and re-lengthening, as well as a less efficient cytosolic calcium clearing and an increased tendency to develop spontaneous twitches. In addition, treatment with Co3O4-NPs strongly increased ROS accumulation and induced nuclear DNA damage in a dose dependent manner. Finally, transmission electron microscopy analysis demonstrated that acute exposure did lead to cellular internalization of NPs. Conclusions: Taken together, our observations indicate that Co3O4-NPs alter cardiomyocyte electromechanical efficiency and intracellular calcium handling, and induce ROS production resulting in oxidative stress that can be related to DNA damage and adverse effects on cardiomyocyte functionality. [ABSTRACT FROM AUTHOR]

Background: Global migration toward Europe is increasing. Providing health assistance to migrants is challenging because numerous barriers limit their accessibility to health services. Migrants may be at a greater risk of developing asthma and receiving lower quality healthcare assistance than non-migrants. We aim to investigate whether immigrants as children and adolescents have higher rates of potentially avoidable hospitalization (PAH) for asthma compared to Italians.Methods: We performed a retrospective longitudinal study using six cohorts of 2-17-year-old residents in North and Central Italy from 01/01/2001 to 31/12/2014 (N = 1,256,826). We linked asthma hospital discharges to individuals using anonymized keys. We estimated cohort-specific age and calendar-year-adjusted asthma PAH rate ratios (HRRs) and 95% confidence intervals (95%CIs) among immigrants compared to Italians. We applied a two-stage random effect model to estimate asthma PAH meta-analytic rate ratios (MHRRs). We analyzed data by gender and geographical area of origin countries.Results: Three thousand three hundred four and 471 discharges for asthma PAH occurred among Italians and immigrants, respectively. Compared to Italians, the asthma PAH cohort-specific rate was higher for immigrant males in Bologna (HRR:2.42; 95%CI:1.53-3.81) and Roma (1.22; 1.02-1.45), and for females in Torino (1.56; 1.10-2.20) and Roma (1.82; 1.50-2.20). Asthma PAH MHRRs were higher only among immigrant females (MHRRs:1.48; 95%CI:1.18-1.87). MHRRs by area of origin were 63 to 113% higher among immigrants, except for Central-Eastern Europeans (0.80; 0.65-0.98).Conclusion: The asthma PAH meta-analytic rate was higher among female children and adolescent immigrants compared to Italians, with heterogeneity among cohorts showing higher cohort-specific PAH also among males, with some differences by origin country. Access to primary care for children and adolescent immigrants should be improved and immigrants should be considered at risk of severe asthma outcomes and consequently targeted by clinicians. [ABSTRACT FROM AUTHOR]

Aim: Critical illness myopathy (CIM) represents a common consequence of modern intensive care, negatively impacting patient health and significantly increasing health care costs; however, there is no treatment available apart from symptomatic and supportive interventions. The chaperone co‐inducer BGP‐15 has previously been shown to have a positive effect on the diaphragm in rats exposed to the intensive care unit (ICU) condition. In this study, we aim to explore the effects of BGP‐15 on a limb muscle (soleus muscle) in response to the ICU condition. Methods: Sprague‐Dawley rats were subjected to the ICU condition for 5, 8 and 10 days and compared with untreated sham‐operated controls. Results: BGP‐15 significantly improved soleus muscle fibre force after 5 days exposure to the ICU condition. This improvement was associated with the protection of myosin from post‐translational myosin modifications, improved mitochondrial structure/biogenesis and reduced the expression of MuRF1 and Fbxo31 E3 ligases. At longer durations (8 and 10 days), BGP‐15 had no protective effect when the hallmark of CIM had become manifest, that is, preferential loss of myosin. Unrelated to the effects on skeletal muscle, BGP‐15 had a strong positive effect on survival compared with untreated animals. Conclusions: BGP‐15 treatment improved soleus muscle fibre and motor protein function after 5 days exposure to the ICU condition, but not at longer durations (8 and 10 days) when the preferential loss of myosin was manifest. Thus, long‐term CIM interventions targeting limb muscle fibre/myosin force generation capacity need to consider both the post‐translational modifications and the loss of myosin. [ABSTRACT FROM AUTHOR]

An accurate potential curve for the bound and quasibound region of the B [sup 1]Π[sub u] state of [sup 7]Li[sub 2] is produced by analyzing high resolution sub-Doppler B [sup 1]Π[sub u]←X [sup 1]Σ[sub g][sup +] excitation spectra in conjunction with lower resolution data of Hessel and Vidal [J. Chem. Phys. 70, 4439 (1979)] and of Russier et al. [J. Mol. Spectrosc. 168, 39 (1994)]. The bound and quasibound part of the curve is generated by the direct fit of molecular energies to a numerical potential; the outermost (repulsive) part of the curve is calculated by an asymptotic method using Coulombic and exchange parameters determined from the 1 [sup 1]Π[sub g] and A [sup 1]Σ[sub u][sup +] states of the lithium dimer. The full potential energy curve of the B [sup 1]Π[sub u] state reproduces all measured energies of f parity, and the widths of the predissociated lines, to within the experimental accuracy. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The E [sup 1]Π, v=1 state of carbon monoxide is studied in high resolution using a tunable and narrowband laser source in the vacuum ultraviolet near 105 nm. Calibration with respect to a reference standard consisting of iodine lines in the visible range, measured by saturated absorption spectroscopy, yields an absolute accuracy of 0.003 cm[sup -1] for the CO resonances. Transition frequencies of the E-X(1,0) band were determined for all six natural isotopomers ([sup 12]C[sup 16]O, [sup 12]C[sup 17]O, [sup 12]C[sup 18]O, [sup 13]C[sup 16]O, [sup 13]C[sup 17]O, and [sup 13]C[sup 18]O) and improved molecular constants derived. Natural lifetime broadening, caused by predissociation was investigated quantitatively for single rotational and (e)-(f ) parity levels. The accidental predissociation phenomena, giving rise to line shifts and broadening, could be explained up to the experimental accuracy in a model based on spin-orbit-coupling between E [sup 1]Π, v=1 and k [sup 3]Π, v=6 states, with a coupling constant of H[sub E,k]=1.88±0.01 cm[sup -1] for all six isotopomers. The overall line broadening parameter Γ[sub E] for the E state, ascribed to interaction with a repulsive [sup 1]Π state, and Γ[sub k] for the k state, were determined as well; the predissociation rates were found to decrease with increasing reduced mass of the isotopomers for both E [sup 1]Π, v=1 and k [sup 3]Π, v=6 states. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Reports that a sub-Doppler experiment involving an effusive beam of lithium dimers and a continuous wave tunable dye laser is used to record the absorption spectrum of the B-X system. Predissociation due to tunneling through the potential barrier of the B state; Interpretation of experimental data according to a semiclassical dynamical model.

Aims: This computational study refines our recently published pacing protocol to measure short-term memory (STM) of cardiac action potential (AP), and apply it to five numerical models of human ventricular AP.Methods and Results: Several formulations of electrical restitution (ER) have been provided over the years, including standard, beat-to-beat, dynamic, steady-state, which make it difficult to compare results from different studies. We discuss here the notion of dynamic ER (dER) by relating it to its steady-state counterpart, and propose a pacing protocol based on dER to measure STM under periodically varying pacing cycle length (CL). Under high and highly variable-pacing rate, all models develop STM, which can be measured over the entire sequence by means of dER. Short-term memory can also be measured on a beat-to-beat basis by estimating action potential duration (APD) adaptation after clamping CL constant. We visualize STM as a phase shift between action potential (AP) parameters over consecutive cycles of CL oscillations, and show that delay between CL and APD oscillation is nearly constant (around 92 ms) in the five models, despite variability in their intrinsic AP properties.Conclusion: dER, as we define it and together with other approaches described in the study, provides an univocal way to measure STM under extreme cardiac pacing conditions. Given the relevance of AP memory for repolarization dynamics and stability, STM should be considered, among other usual biomarkers, to validate and tune cardiac AP models. The possibility of extending the method to in vivo cellular and whole organ models can also be profitably explored. [ABSTRACT FROM AUTHOR]

The aerosol optical characteristics in the urban area of Rome were retrieved over a period of 7 years from March to September 2010–2016. The impact of aerosol single scattering albedo (SSA), optical depth (AOD), estimated at 400 nm, and Ångström exponent on the ultraviolet (UV) index has been analyzed. Aerosol optical properties are provided by a PREDE-POM sun-sky radiometer of the ESR/SKYNET network and the UV index values were retrieved by a Brewer spectrophotometer both located in Rome. Chemical characterization of urban PM10 (particulate matter 10 micrometers or less in diameter) samples, collected during the URBan Sustainability Related to Observed and Monitored Aerosol (URBS ROMA) intensive filed campaign held in summer 2011 in the same site, was performed. PM macro-components were grouped in order to evaluate the contribution of the main macro-sources (SOIL, SEA, SECONDARY INORGANIC, ORGANICS and TRAFFIC) and the analysis of the modulation of their concentration was found to strongly affects the absorption capability of the atmosphere over Rome. The surface forcing efficiency, provided by the decreasing trend of UV index with AOD, which is the primary parameter affecting the surface irradiance, was found very significant, probably masking the dependence of UV index on SSA and Ångström exponents. Moreover it was found greater for larger particles and with a more pronounced slope at the smaller solar zenith angle. In Rome large particles are generally less absorbing since related to the presence of SOIL and SEA components in the atmosphere. The former contribution was found much higher in summer months because of the numerous episodes of Saharan dust transport. [ABSTRACT FROM AUTHOR]

Vertical profiles of the particle backscattering coefficient at 355, 532 and 1064 nm measured by the University of Basilicata Raman lidar system (BASIL) have been compared with simulated particle backscatter profiles obtained through a Mie scattering code based on the use of simultaneous and almost co-located profiles provided by an airborne optical particle counter. Measurements were carried out during dedicated flights of the French research aircraft ATR42 in the framework of the European Facility for Airborne Research (EUFAR) project "WaLiTemp", as part of the Hydrological Cycle in the Mediterranean Experiment – Special Observation Period 1 (HyMeX-SOP1). Results from two selected case studies are reported and discussed in the paper, and a dedicated analysis approach is illustrated and applied to the dataset. Results reveal a good agreement between measured and simulated multi-wavelength particle backscattering profiles. Specifically, simulated and measured particle backscattering profiles at 355 and 532 nm for the second case study are found to deviate less than 15 % (mean value =5.9 %) and 50 % (mean value =25.9 %), respectively, when considering the presence of a continental–urban aerosol component, while slightly larger deviation values are found for the first study. The reported good agreement between measured and simulated multi-wavelength particle backscatter profiles testifies to the ability of multi-wavelength Raman lidar systems to infer aerosol types at different altitudes. [ABSTRACT FROM AUTHOR]

We have studied v=0 and v=1 levels of the E 1Π state of CO in excitation from the ground state by one- and two-photon transitions, thus probing e and f Λ-doublet components. New accidental predissociations were found in the E 1Π, v=0 state for high J values (Je=41, 44 for 12C16O and Je=41, 50 for 13C16O). The predissociation phenomenon in the E 1Π, v=1 state at J=7 was reinvestigated and for both e and f components also J=9, 10, and 12 were found to be perturbed. Perturbations by all three spin components of a k 3Π, v=5 state were deduced. Furthermore the accidental predissociation in E 1Π, v=0 Je=31 was reinvestigated. Measurements of spectral line shifts were modeled assuming a spin-orbit coupling between E 1Π and the 3Π1 component of the k 3Π state. Relative predissociation lifetimes of k 3Π, v=3 and 5 with respect to E 1Π, v=0 and v=1 are deduced from an analysis of observed intensity effects. For the E 1Π, v=1 state rotational state dependent lifetimes were determined at low-J values. Line positions of CO lines were calibrated on an absolute frequency scale within 0.05 cm-1 against the tellurium and iodine standard in the visible. Accurate molecular constants for the E 1Π, v=0 and v=1 states are determined for both 12C16O and 13C16O. The E 1Π, v=1 state of 12C17O is observed for the first time. © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Vertical profiles of particle backscattering coefficient at 355, 532 and 1064 nm measured by the lidar Raman system BASIL have been compared with simulated particle backscatter profiles obtained through a Mie scattering code based on the use of simultaneous and almost co-located profiles provided by an air-borne optical particle counter. Measurements were carried out during dedicated flights of the French research aircraft ATR42 in the frame of the European Facility for Airborne Research (EUFAR) Project WaLiTemp, as part of the Hydrological Cycle in the Mediterranean Experiment - Special Observation Period 1 (HyMeX-SOP1). Results from two selected case studies are reported and discussed in the paper and two slightly different analysis approaches are illustrated and applied to the dataset. Results reveal a good agreement between measured and simulated multi-wavelength particle backscattering profiles. Specifically, simulated and measured particle backscattering profiles at 355 and 532 nm are found to deviate less than 15 % (mean value = 7 %) and 50 % (mean value = 30 %), respectively, when considering the presence of a Continental/Urban aerosol component. Reported results reveal a good agreement between measured and simulated multi-wavelength particle backscatter profiles, which ultimately testifies lidar ability to infer the aerosol type from these measurements. [ABSTRACT FROM AUTHOR]

Purpose The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. Participants IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. Findings to date The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. Future plans We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts. [ABSTRACT FROM AUTHOR]

This paper illustrates measurements carried out by the Raman lidar BASIL in the frame of the HD(CP)2 Observational Prototype Experiment (HOPE), revealing the presence of a clear-air dark band phenomenon (i.e. a minimum in lidar backscatter echoes) in the upper portion of the convective boundary layer. The phenomenon is clearly distinguishable in the lidar backscatter echoes at 532 and 1064 nm, as well as in the particle depolarisation data. This phenomenon is attributed to the presence of lignite aerosol particles advected from the surrounding open pit mines in the vicinity of the measuring site. The paper provides evidence of the phenomenon and illustrates possible interpretations for its occurrence. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that borderline personality disorder (BPD) is associated with neuropsychological deficits and there is evidence that the neurocognitive profile of patients with BPD may be related to the outcome of this disorder. The aim of this study was to investigate the feasibility and the effectiveness of a cognitive remediation intervention in patients with BPD. Thirty patients with a DSM-IV-TR diagnosis of BPD were assessed on clinical, neuropsychological and functional outcome measures at baseline and after 16 weeks of a computer-assisted cognitive remediation (CACR) intervention or treatment as usual (TAU). Patients who received CACR showed a greater improvement in working memory and psychosocial functioning measures than patients treated with TAU. Symptom severity was not significantly affected by CACR treatment. The findings of this pilot study suggest the feasibility and potential effectiveness on specific cognitive domains, but modest clinical usefulness of a computerised modality of cognitive remediation in the treatment of BPD. [ABSTRACT FROM AUTHOR]