Search Results (26)

Background: Therapeutic drug monitoring (TDM) of infliximab (IFX) and adalimumab (ADL) mainly relies on the use of enzyme-linked immunosorbent assays (ELISA). More recently, rapid assays have been developed and validated to reduce turnaround time (TAT). Here, we compared IFX and ADL concentrations measured with both ELISA and a new fluorescence-based lateral flow immunoassay (AFIAS). Methods: In serum samples from pediatric patients, IFX and ADL drug levels, and total anti-IFX antibodies were measured using clinically validated ELISA kits (Immundiagnostik AG). Samples were further analyzed using a new rapid assay (AFIAS, Boditech Med Inc.) to measure drug levels and total anti-IFX antibodies. Results: Spearman’s correlation coefficients (rho) were 0.98 [95% confidence interval (CI) 0.97 to 0.99] for IFX (p < 0.001) and 0.83 (95% CI 0.72 to 0.90) for ADL (p < 0.001). Calculated % bias was −14.09 (95% Limits of agreement, LoA, −52.83 to 24.66) for IFX and 15.79 (LoA −37.14 to 68.73) for ADL. For the evaluation of total anti-IFX antibodies, we did not collect sufficient data to establish a statistically significant correlation between AFIAS and ELISA. The inter-rater agreement showed a “substantial” and a “moderate” agreement for IFX and ADL, respectively. Conclusions: Our results show that the AFIAS assay has an accuracy and analytical performance comparable to that of the ELISA method used for TDM of IFX and ADL. Therefore, the introduction of this device into routine clinical practice could provide results more quickly and with similar accuracy as ELISA, allowing clinicians to rapidly formulate clinical decisions. Full article

Aerosol vertical stratification significantly influences the Earth’s radiative balance and particulate-matter-related air quality. Continuous vertically resolved observations remain scarce compared to surface-level and column-integrated measurements. This work presents and makes available a novel, long-term (2016–2022) aerosol dataset derived from continuous (24/7) vertical profile observations from three selected stations (Aosta, Rome, Messina) of the Italian Automated Lidar-Ceilometer (ALC) Network (ALICENET). Using original retrieval methodologies, we derive over 600,000 quality-assured profiles of aerosol properties at the 15 min temporal and 15 metre vertical resolutions. These properties include the particulate matter mass concentration (PM), aerosol extinction and optical depth (AOD), i.e., air quality legislated quantities or essential climate variables. Through original ALICENET algorithms, we also derive long-term aerosol vertical layering data, including the mixed aerosol layer (MAL) and elevated aerosol layers (EALs) heights. Based on this new dataset, we obtain an unprecedented, fine spatiotemporal characterisation of the aerosol vertical distributions in Italy across different geographical settings (Alpine, urban, and coastal) and temporal scales (from sub-hourly to seasonal). Our analysis reveals distinct aerosol daily and annual cycles within the mixed layer and above, reflecting the interplay between site-specific environmental conditions and atmospheric circulations in the Mediterranean region. In the lower troposphere, mixing processes efficiently dilute particles in the major urban area of Rome, while mesoscale circulations act either as removal mechanisms (reducing the PM by up to 35% in Rome) or transport pathways (increasing the loads by up to 50% in Aosta). The MAL exhibits pronounced diurnal variability, reaching maximum (summer) heights of >2 km in Rome, while remaining below 1.4 km and 1 km in the Alpine and coastal sites, respectively. The vertical build-up of the AOD shows marked latitudinal and seasonal variability, with 80% (30%) of the total AOD residing in the first 500 m in Aosta-winter (Messina-summer). The seasonal frequency of the EALs reached 40% of the time (Messina-summer), mainly in the 1.5–4.0 km altitude range. An average (wet) PM > 40 μg m⁻³ is associated with the EALs over Rome and Messina. Notably, 10–40% of the EAL-affected days were also associated with increased PM within the MAL, suggesting the entrainment of the EALs in the mixing layer and thus their impact on the surface air quality. We also integrated ALC observations with relevant, state-of-the-art model reanalysis datasets (ERA5 and CAMS) to support our understanding of the aerosol patterns, related sources, and transport dynamics. This further allowed measurement vs. model intercomparisons and relevant examination of discrepancies. A good agreement (within 10–35%) was found between the ALICENET MAL and the ERA5 boundary layer height. The CAMS PM₁₀ values at the surface level well matched relevant in situ observations, while a statistically significant negative bias of 5–15 μg m⁻³ in the first 2–3 km altitude was found with respect to the ALC PM profiles across all the sites and seasons. Full article

Fabry disease (FD) is a rare X-linked lysosomal storage disorder with a broad spectrum of clinical manifestations, including severe complications, such as end-stage renal disease, hypertrophic cardiomyopathy, and cerebrovascular disease. Enzyme replacement therapy (ERT), when initiated early, has been shown to reduce the incidence of severe events and slow disease progression. In the classic form, characterized by the absence of α-galactosidase A (α-Gal A) enzyme activity, diagnosis is straightforward. However, when residual activity is present, the delayed and less obvious presentation can make diagnosis more challenging. Ophthalmological alterations, which can be detected through non-invasive examinations may play a crucial role in correctly assessing the patient in terms of diagnosis and prognosis, particularly in these atypical cases. Recognizing these ocular signs allows for timely intervention with ERT, leading to improved patient outcomes. This review highlights the importance of ophthalmological findings in FD, emphasizing their role in diagnosis and treatment planning. By raising awareness among ophthalmologists and healthcare specialists, this review aims to improve disease management, offering tools for early detection and better long-term prognosis in patients with FD. Full article

Polar stratospheric clouds (PSCs) form in polar regions, typically between 15 and 25 km above mean sea level, when the local temperature is sufficiently low. PSCs play an important role in the ozone chemistry and the dehydration and denitrification of the stratosphere. Lidars with a depolarization channel may be used to detect and classify different classes of PSCs. The main PSC classes are water ice, nitric acid trihydrate (NAT), and supercooled ternary solutions (STSs), the latter being liquid droplets consisting of water, nitric acid, and sulfuric acid. PSCs have been observed at the lidar observatory at Concordia Station from 2014 onward. The harsh environmental conditions at Concordia during winter render successful lidar operation difficult. To facilitate the operation of the observatory, several measures have been put in place to achieve an almost complete remote control of the system. PSC occurrence is strongly correlated with local temperatures and is affected by dynamics, as the PSC coverage during the observation season shows. PSC observations in 2021 are shown as an example of the capability and functionality of the lidar observatory. A comparison of the observations with the satellite-borne CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) lidar has been made to demonstrate the quality of the data and their representativeness for the Antarctic Plateau. Full article

Imaging disdrometers are widely used in field campaigns to provide information on the shape of hydrometeors, together with the diameter and the fall velocity, which can be used to derive information on the shape–size relations of hydrometeors. However, due to their higher price compared to laser disdrometers, their use is limited to scientific research purposes. The 3D stereo (3DS) is a commercial imaging disdrometer recently made available by Thies Clima and on which there are currently no scientific studies in the literature. The most innovative feature of the 3DS is its ability in capturing images of the particles passing through the measurement volume, crucial to provide an accurate classification of hydrometeors based on information about their shape, especially in the case of solid precipitation. In this paper. the performance of the new device is analyzed by comparing 3DS with the Laser Precipitation Monitor (LPM) from the same manufacturer, which is a known laser disdrometer used in many research works. The data used in this paper were obtained from measurements of the two instruments carried out at the Casale Calore site in L’Aquila during the CORE-LAQ (Combined Observations of Radar Experiments in L’Aquila) campaign. The objective of the comparison analysis is to analyze the differences between the two disdrometers in terms of hydrometeor classification, number and falling speed of particles, precipitation intensity, and total cumulative precipitation on an event basis. As regards the classification of precipitation, the two instruments are in excellent agreement in identifying rain and snow; greater differences are observed in the case of particles in mixed phase (rain and snow) or frozen phase (hail). Due to the different measurement area of the two disdrometers, the 3DS generally detects more particles than the LPM. The performance differences also depend on the size of the hydrometeors and are more significant in the case of small particles, i.e., D < 1 mm. In the case of rain events, the two instruments are in agreement with respect to the terminal velocity in still air predicted by the Gunn and Kinzer model for drops with a diameter of less than 3 mm, while, for larger particles, terminal velocity is underestimated by both the disdrometers. The agreement between the two instruments in terms of total cumulative precipitation per event is very good. Regarding the 3DS ability to capture images of hydrometeors, the raw data provide, each minute, from one to four images of single particles and information on their size and type. Their number and coarse resolution make them suitable to support only qualitative analysis of the shape of precipitating particles. Full article

Clouds cover substantial parts of the Earth’s surface and they are one of the most essential components of the global climate system impacting the Earth’s radiation balance as well as the water cycle redistributing water around the globe as precipitation. Therefore, continuous observation of clouds is of primary interest in climate and hydrological studies. This work documents the first efforts in Italy in remote sensing clouds and precipitation using a combination of K- and W-band (24 and 94 GHz, respectively) radar profilers. Such a dual-frequency radar configuration has not been widely used yet, but it could catch on in the near future given its lower initial cost and ease of deployment for commercially available systems at 24 GHz, with respect to more established configurations. A field campaign running at the Casale Calore observatory at the University of L’Aquila, Italy, nestled in the Apennine mountain range is described. The campaign features are preceded by a review of the literature and the underpinning theoretical background that might help newcomers, especially in the Italian community, to approach cloud and precipitation remote sensing. This activity takes place in interesting time for radar sensing clouds and precipitation, stimulated both by the launch of the ESA/JAXA EarthCARE satellite missions scheduled in 2024, which will have on-board, among other instruments, a W-band Doppler cloud radar and the proposal of new missions using cloud radars currently undergoing their feasibility studies (e.g., WIVERN and AOS in Europe and Canada, and U.S., respectively). Full article

SET-M33 is a synthetic peptide that is being developed as a new antibiotic against major Gram-negative bacteria. Here we report two in vivo studies to assess the toxicity and efficacy of the peptide in a murine model of pulmonary inflammation. First, we present the toxicity study in which SET-M33 was administered to CD-1 mice by snout inhalation exposure for 1 h/day for 7 days at doses of 5 and 20 mg/kg/day. The results showed adverse clinical signs and effects on body weight at the higher dose, as well as some treatment-related histopathology findings (lungs and bronchi, nose/turbinates, larynx and tracheal bifurcation). On this basis, the no observable adverse effect level (NOAEL) was considered to be 5 mg/kg/day. We then report an efficacy study of the peptide in an endotoxin (LPS)-induced pulmonary inflammation model. Intratracheal administration of SET-M33 at 0.5, 2 and 5 mg/kg significantly inhibited BAL neutrophil cell counts after an LPS challenge. A significant reduction in pro-inflammatory cytokines, KC, MIP-1α, IP-10, MCP-1 and TNF-α was also recorded after SET-M33 administration. Full article

Background: The recent introduction of ecological momentary assessment (EMA) smartphone-based strategies has allowed achieving some interesting data on the frequency of different awake bruxism (AB) behaviors reported by an individual in the natural environment. Objective: The present paper aims to review the literature on the reported frequency of AB based on data gathered via smartphone EMA technology. Methods: On September 2022, a systematic search in the Pubmed, Scopus and Google Scholar databases was performed to identify all peer-reviewed English-language studies assessing awake bruxism behaviors using a smartphone-based Ecological Momentary Assessment. The selected articles were assessed independently by two authors according to a structured reading of the articles’ format (PICO). Results: A literature search, for which the search terms “Awake Bruxism” and “Ecological Momentary Assessment” were used, identified 15 articles. Of them, eight fulfilled the inclusion criteria. The results of seven studies using the same smartphone-based app reported a frequency of AB behaviors in the range between 28.3 and 40% over one week, while another investigation adopted a different smartphone-based EMA approach via WhatsApp using a web-based survey program and reported an AB frequency of 58.6%. Most included studies were based on convenience samples with limited age range, highlighting the need for more studies on other population samples. Conclusions: Despite the methodological limits, the results of the reviewed studies provide a standpoint for comparison for future studies on the epidemiology of awake bruxism behaviors. Full article

Self-reported awake bruxism (AB) has been associated with temporomandibular disorders (TMD). However, the daily amount of AB behavior has not been quantified in pain patients. Therefore, this study aimed to assess AB frequency in patients with myofascial pain and temporomandibular joint (TMJ) pain and compare it to a group of pain-free individuals. Eighty-four individuals belonging to either a TMD group (n = 54) or a healthy control group (n = 30) were selected. AB frequency was obtained by ecological momentary assessment with a dedicated smartphone application that sent sound alerts at random intervals during the day for one week. Upon receiving the alert, the volunteer reported the current muscular condition and/or the teeth position, i.e., relaxed jaw muscle, jaw bracing, teeth contact, teeth clenching, or teeth grinding. Data were evaluated by independent t-test (α = 0.05). During the seven days, AB frequency was 62.1% ± 26.8% for TMD patients and 36.2% ± 27.3% for pain-free subjects (p < 0.001). Mandible bracing was most common in the TMD group (p < 0.001), while teeth contact, clenching, and grinding did not differ between groups. Moreover, no differences were found in AB frequency between myofascial pain and TMJ pain patients. Therefore, TMD patients have higher AB frequency characterized by jaw bracing, irrespective of pain location. Full article

Objective: The instrumental measurement of electromyographic (EMG) activity in the natural environment is the best strategy available to collect information on bruxism. The twofold aim of this study was to (1) introduce and discuss a novel EMG device for the assessment of awake (AB) and sleep bruxism (SB) in the home environment over 24 h and (2) present some preliminary data. Methods: Fifteen healthy volunteers (eight males and seven females; mean age: 48.2 ± 4.1 years) underwent 24 h EMG recording trials of their masseter muscle activity (MMA) with a miniaturized wireless device. This device allowed us to measure the durations of the different phases of the recordings (total duration, awake time, sleep time, and electrode dislodgement time) as well as the bruxism time index (BTI) and bruxism work index (BWI) for both the waking and sleeping hours. Results: For the healthy volunteers, on average, the bruxism work index (BWI) values were 0.4 ± 0.2 and 0.1 ± 0.1 for awake and sleep, respectively, while the mean bruxism time index (BTI) values were 0.9 ± 0.5 for awake and 0.3 ± 0.1 for sleep. Conclusions: This investigation describes the technical features of a novel EMG recording device that permits the evaluation of masseter muscle activity in the home environment over 24 h. For the first time, a dedicated elaboration of the EMG signal allowed an assessment of muscle work and not just a count of purported SB/EMG events. Clinical significance: Based on the multidisciplinary approach in the study of bruxism, such a methodology, thanks to its peculiar features, will allow researchers and clinicians to monitor the epidemiology of MMA and delve deeper into the awake and sleep bruxism correlates for tailored management in clinical settings. Full article

Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction of a biocompatible nanosystem where the antimicrobial peptide SET-M33 is encapsulated within polymeric nanoparticles of poly(lactide-co-glycolide) (PLGA) conjugated with polyethylene glycol (PEG). This system was conceived for better delivery of the peptide to the lungs by aerosol. The encapsulated peptide showed prolonged antibacterial activity, due to its controlled release, and much lower toxicity than the free molecule. The peptide-based nanosystem killed Pseudomonas aeruginosa in planktonic and sessile forms in a dose-dependent manner, remaining active up to 72 h after application. The encapsulated peptide showed no cytotoxicity when incubated with human bronchial epithelial cells from healthy individuals and from cystic fibrosis patients, unlike the free peptide, which showed an EC50 of about 22 µM. In vivo acute toxicity studies in experimental animals showed that the peptide nanosystem did not cause any appreciable side effects, and confirmed its ability to mitigate the toxic and lethal effects of free SET-M33. Full article

Over the years, several tools have been proposed to measure oral behaviours (OB). Recently, a smartphone-based application for ecological momentary assessment (EMA) has been introduced to collect real-time data on waking-time OB. The aim of this study was to compare the self-reported frequency of OB by means of a standardised questionnaire with that recorded with a smartphone-based application for EMA. A total of 151 participants, recruited from the general population, were invited to fill in the Oral Behaviour Checklist (OBC). Scores for four questions concerning grinding, clenching, tooth contact, and mandible bracing were computed. Afterwards, participants were provided with a smartphone application for prolonged real-time reporting of OB. One-way analysis of variance (ANOVA) and a general linear mixed model (GLMM) were used to compare the responses to each OBC question with the frequencies of the same condition recorded with the EMA. Results showed significant association between OBC responses and the EMA recordings. In particular, increased frequencies of clenching, grinding, and teeth contact were recorded by individuals who provided higher OBC scores. On the other hand, a nonlinear association was observed for “mandible bracing”, pointing out difficulties in the comprehension of this condition. Full article

Endodontic and periodontal disease are conditions of infectious origin that can lead to tooth loss or develop into systemic hyperinflammation, which may be associated with a wide variety of diseases, including cardiovascular. Endodontic and periodontal treatment often relies on antibiotics. Since new antimicrobial resistances are a major threat, the use of standard antibiotics is not recommended when the infection is only local. Antimicrobial peptides were recently demonstrated to be valid alternatives for dental treatments. The antimicrobial peptide M33D is a tetrabranched peptide active against Gram-negative and Gram-positive bacteria. It has a long life, unusual for peptides, because its branched form provides resistance to proteases. Here the efficacy of M33D and of its analog M33i/l as antibiotics for local use in dentistry was evaluated. M33D and M33i/l were active against reference strains and multidrug-resistant clinical isolates of Gram-negative and Gram-positive species. Their minimum inhibitory concentration against different strains of dental interest was between 0.4 and 6.0 μM. Both peptides acted rapidly on bacteria, impairing membrane function. They also disrupted biofilm effectively. Disinfection of the root canal is crucial for endodontic treatments. M33D and M33i/l reduced E. faecalis colonies to one-twentieth in a dentin slices model reproducing root canal irrigation. They both captured and neutralized lipopolysaccharide (LPS), a bacterial toxin responsible for inflammation. The release of IL-1β and TNFα by LPS-stimulated murine macrophages was reduced by both peptides. Human cardiac fibroblasts respond to different insults with the release of proinflammatory cytokines, and consequently, they are considered directly involved in atherogenic cardiovascular processes, including those triggered by infections. The presence of M33D and M33i/l at MIC concentration reduced IL6 release from LPS- stimulated human cardiac fibroblasts, hence proving to be promising in preventing bacteria-induced atherogenesis. The two peptides showed low toxicity to mammalian cells, with an EC50 one order of magnitude higher than the average MIC and low hemolytic activity. The development of antimicrobial peptides for dental irrigations and medication is a very promising new field of research that will provide tools to fight dental infections and their severe consequences, while at the same time protecting standard antibiotics from new outbreaks of antimicrobial resistance. Full article

Awake bruxism (AB) is differentiated from sleep bruxism (SB) by the differences in etiology, comorbidities, and consequences related to the different spectrum of muscle activities exerted in relation to the different circadian manifestations. Furthermore, less literature data are available on AB than on SB. The introduction of ecological momentary assessment (EMA) strategies has allowed for collecting valuable data on the frequency of the different activities reported by an individual in his/her natural environment. This strategy has been further improved with the recent use of smartphone technologies. Recent studies have described an average frequency of AB behaviors, within the range of 23–40% for otherwise healthy young adults. An association between AB and some psychological traits has emerged, and the findings have indicated that patients with musculoskeletal symptoms (e.g., temporomandibular joint and/or muscle pain, muscle stiffness, and fatigue) report higher AB frequencies. Preliminary data suggest that muscle bracing and teeth contact are the most commonly reported behaviors, while teeth clenching is much less frequently reported than commonly believed previously. Report of teeth grinding during wakefulness is almost absent. This paper has critically reviewed the currently available approaches for the assessment of AB. In addition, some future perspectives and suggestions for further research have been provided. Full article

The prevalence of awake bruxism (AB) has been reported as being 30%, with sleep bruxism (SB) at 9–15%. Most studies have focused on SB, emphasizing the importance of AB research. For epidemiological evaluations of AB, a smartphone application based on ecological momentary assessment (EMA) was introduced. The aims of this multi-center study were: (1) to investigate how well lay subjects comprehend the AB terminology used in the smartphone application, and (2) to find out whether professional instruction improved their comprehension. The study population consisted of lay subjects from Italy, Portugal, and Finland comprising 307 individuals (156 men, 151 women; 18–86 years). Subjects first completed a five-item questionnaire about the meanings of the five AB terms used in the smartphone application. Each question offered four answer options, with one being correct. Immediately afterwards, the meanings of the terms were instructed. Lastly, the subjects were re-tested with the same questionnaire. In Finland and Italy, the re-tested correct answer scores for the single terms were at 89–97% per term. Improved comprehension was seen across sex, education, and age groups. In the Portuguese data, no improvement was found. Significant differences were found between countries in the improved scores for all terms that were correct following the instruction (Finland, 16.3% to 72.1%; Italy, 32.3% to 83.8%; Portugal, 23.1% to 33.7%) (p < 0.001). In conclusion, standardized instruction on AB terminology prior to EMA is recommended to improve the reliability of collected data. Full article