A trip in voice phytotheraphy: TRPA1 ion channel as a target for bioactive compounds in herbal remedies for voice care

Voice is the sound we produce to communicate meanings and ideas and has a capital importance in human social development. Herbs have been used for voice care since ancient times and many herbal remedies are still in use, both as folk medicine and as sources of botanicals used in commercial products. In Europe Sisymbrium officinale (L.) Scop (the "singers'plant\u201d) is the most popular herbal remedy for voice care, but many other plants are employed in phytopreparations. The mechanisms of action of these botanicals include anti-bacterial, anti-inflammatory, mucolytic, antinociceptive and other general activities; nevertheless, mechanisms that could be specifically referred to voice are often unknown. We collected information on plants used worldwide for voice care; the plants have been organized in a database (Herbs for Voice Database) and classified according to the bioactive compounds, their molecular targets and the pathologies they are recommended for. The data were analyzed with the aim to identify some possible common mechanism of action and the molecular targets involved. The analysis of data shows that an important pathway involves the somatosensory TRPA1 (Transient Receptor Potential Ankyrin type 1) ion channel, a well-known mediator of irritation, inflammatory and neurogenic pain. Agonists of this ion channel have been identified in 27 over 44 plants, corresponding to 61,3% of the plants in the database. Also TRPM8 (Transient Receptor Potential Melastatin type 8), involved in the perception of coolness, was identified among the molecular targets. This finding reinforces the hypothesis that these somatosensory ion channels could be involved in relevant mechanisms of action of these traditional remedies and open new perspectives in the rational study of voice phytopharmacology and therapy. This research was funded by FONDAZIONE CARIPLO (Milano, I), University of Milano (I) and Conservatorio di Musica G. Verdi (Milano, I), grant number 2017-1653

Herbs for voice database : developing a rational approach to the study of herbal remedies used in voice care

Herbs have been used for voice care since ancient times and many herbal remedies are still in use in every geographical areas and cultures, both as traditional medicine and as sources of botanicals used in commercial products. Many of these plants are used as extracts and other phytopreparates, and a full phytochemical analysis is sometimes incomplete or lacking. The mechanisms of action of these botanicals include antibacterial, antiinflammatory, mucolytic, and other general activities; nevertheless, mechanisms that could be specifically referred to voice are often unknown, as well as the corresponding molecular targets and therefore a rational approach in the use of these remedies is hard to be applied by phoniatricians. To address this problem, we collected information on plants used for voice care from several different geographical areas, using both literature data and a pool of contributors from an international network of artistic phoniatrics and vocologists. The plants have been organized in a database (Herbs for Voice Database) and classified according to the natural compounds contained in them, their molecular targets and the pathologies they are recommended for. This first database contains 44 plants, 101 phytocompounds, and 32 recognized molecular targets. The distribution of herbs and phytocompounds according to the botanical families, their known biological activity, traditional uses, and molecular targets were analyzed. In particular, data analysis shows that the somatosensory and pain receptor Transient Receptor Potential Ankyrin 1 ion channel is targeted by a large number of different phytochemicals contained in the herbs for voice, and could therefore be involved in a mechanism of action common to many plants

Effects of temperature on flood forecasting: analysis of an operative case study in Alpine basins

Abstract. In recent years the interest in the forecast and prevention of natural hazards related to hydro-meteorological events has increased the challenge for numerical weather modelling, in particular for limited area models, to improve the quantitative precipitation forecasts (QPF) for hydrological purposes. After the encouraging results obtained in the MAP D-PHASE Project, we decided to devote further analyses to show recent improvements in the operational use of hydro-meteorological chains, and above all to better investigate the key role played by temperature during snowy precipitation. In this study we present a reanalysis simulation of one meteorological event, which occurred in November 2008 in the Piedmont Region. The attention is focused on the key role of air temperature, which is a crucial feature in determining the partitioning of precipitation in solid and liquid phase, influencing the quantitative discharge forecast (QDF) into the Alpine region. This is linked to the basin ipsographic curve and therefore by the total contributing area related to the snow line of the event. In order to assess hydrological predictions affected by meteorological forcing, a sensitivity analysis of the model output was carried out to evaluate different simulation scenarios, considering the forecast effects which can radically modify the discharge forecast. Results show how in real-time systems hydrological forecasters have to consider also the temperature uncertainty in forecasts in order to better understand the snow dynamics and its effect on runoff during a meteorological warning with a crucial snow line over the basin. The hydrological ensemble forecasts are based on the 16 members of the meteorological ensemble system COSMO-LEPS (developed by ARPA-SIMC) based on the non-hydrostatic model COSMO, while the hydrological model used to generate the runoff simulations is the rainfall–runoff distributed FEST-WB model, developed at Politecnico di Milano

Application of an early warning to detect enteropathies in intensive broiler farming

Remote and wearable sensors can be combined with smart algorithms to continuously monitor a wide range of animal responses linked with stress, health status and welfare. The idea of real time monitoring assumes a simple way to measure variable that can give an early warning for the farmer providing clear and suitable alerts to help them in their routine. The prompt reaction to any change in health, welfare and productive status is the key for the reduction in drugs usage and for the improvement of animal wellbeing. In intensive poultry farms, enteric disorders represent a major health issue; these pathologies could be multifactorial and are a major cause of performances reduction. Monitoring poultry health status takes a key role for management to reduce chemicals/drugs and their costs. Nowadays, the preventive use of antibiotics in intensive farming system is common and this practice could lead to the spreading of drugs in the environment, contributing to the phenomenon of antibiotic resistance. Due to the high priority of this issue, it is of great importance the early detection of any health problem in intensive farming. Precision Livestock Farming, through the combination of cheap technologies and specific algorithms, can provide valuable information for farmers starting from the huge amount of data collected in real time at farm level. This study was aimed to the application of a PLF diagnostic tool, sensible to the variation of volatile organic compounds, to promptly recognize enteric problems in intensive farming, supporting veterinarians and enabling specific treatments in case of disease

Digital device in postextraction implantology : a clinical case presentation

Aim. The aim of this work is to describe a case of immediate implant placement after extraction of the upper right first premolar, with the use of CAD/CAM technology, which allows an early digital impression of the implant site with an intraoral scanner (MHT 3D Progress, Verona, Italy). Case Report. A 46-year-old female was referred with a disorder caused by continuous debonding of the prosthetic crown on the upper right first premolar. Clinically, there were no signs, and the evaluation of the periapical radiograph showed a fracture of the root, with a mesial well-defined lesion of the hard tissue of the upper right first premolar, as the radiolucent area affected the root surface of the tooth. It was decided, in accordance with the patient, that the tooth would be extracted and the implant (Primer, Edierre implant system, Genoa, Italy) with diameter of 4.2mm and length of 13mm would be inserted. After the insertion of the implant, it was screwed to the scan abutment, and a scan was taken using an intraoral scanner (MHT 3D Progress, Verona, Italy). The scanned images were processed with CAD/CAM software (Exocad DentalCAD, Darmstadt, Germany) and the temporary crown was digitally drawn (Dental Knowledge, Milan, Italy) and then sent to the milling machine for production with a composite monoblock. After 4 months, when the implant was osteointegrated, it was not necessary to take another dental impression, and the definitive crown could be screwed in. Conclusion. The CAD/CAM technology is especially helpful in postextraction implant for aesthetic rehabilitation, as it is possible to immediately fix a provisional crown with an anatomic shape that allows an optimal healing process of the tissues. Moreover, the removal of healing abutments, and the use of impression copings, impression materials, and dental stone became unnecessary, enabling the reduction of the chair time, component cost, and patient's discomfort. However, it is still necessary for scientific research to continue to carry out studies on this procedure, in order to improve the accuracy, the reliability, and the reproducibility of the results

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

Challenging GRB models through the broadband dataset of GRB060908

Context: Multiwavelength observations of gamma-ray burst prompt and afterglow emission are a key tool to disentangle the various possible emission processes and scenarios proposed to interpret the complex gamma-ray burst phenomenology. Aims: We collected a large dataset on GRB060908 in order to carry out a comprehensive analysis of the prompt emission as well as the early and late afterglow. Methods: Data from Swift-BAT, -XRT and -UVOT together with data from a number of different ground-based optical/NIR and millimeter telescopes allowed us to follow the afterglow evolution from about a minute from the high-energy event down to the host galaxy limit. We discuss the physical parameters required to model these emissions. Results: The prompt emission of GRB060908 was characterized by two main periods of activity, spaced by a few seconds of low intensity, with a tight correlation between activity and spectral hardness. Observations of the afterglow began less than one minute after the high-energy event, when it was already in a decaying phase, and it was characterized by a rather flat optical/NIR spectrum which can be interpreted as due to a hard energy-distribution of the emitting electrons. On the other hand, the X-ray spectrum of the afterglow could be fit by a rather soft electron distribution. Conclusions: GRB060908 is a good example of a gamma-ray burst with a rich multi-wavelength set of observations. The availability of this dataset, built thanks to the joint efforts of many different teams, allowed us to carry out stringent tests for various interpretative scenarios showing that a satisfactorily modeling of this event is challenging. In the future, similar efforts will enable us to obtain optical/NIR coverage comparable in quality and quantity to the X-ray data for more events, therefore opening new avenues to progress gamma-ray burst research.Comment: A&A, in press. 11 pages, 5 figure

A survey of clinical features of allergic rhinitis in adults

Background: Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods: The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18–45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results: Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. . Conclusions: These fndings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed

Multi-wavelength observations of the energetic GRB 080810: detailed mapping of the broadband spectral evolution

GRB 080810 was one of the first bursts to trigger both Swift and the Fermi Gamma-ray Space Telescope. It was subsequently monitored over the X-ray and UV/optical bands by Swift, in the optical by ROTSE and a host of other telescopes and was detected in the radio by the VLA. The redshift of z= 3.355 +/- 0.005 was determined by Keck/HIRES and confirmed by RTT150 and NOT. The prompt gamma/X-ray emission, detected over 0.3-10^3 keV, systematically softens over time, with E_peak moving from ~600 keV at the start to ~40 keV around 100 s after the trigger; alternatively, this spectral evolution could be identified with the blackbody temperature of a quasithermal model shifting from ~60 keV to ~3 keV over the same time interval. The first optical detection was made at 38 s, but the smooth, featureless profile of the full optical coverage implies that this originated from the afterglow component, not the pulsed/flaring prompt emission. Broadband optical and X-ray coverage of the afterglow at the start of the final X-ray decay (~8 ks) reveals a spectral break between the optical and X-ray bands in the range 10^15 - 2x10^16 Hz. The decay profiles of the X-ray and optical bands show that this break initially migrates blueward to this frequency and then subsequently drifts redward to below the optical band by ~3x10^5 s. GRB 080810 was very energetic, with an isotropic energy output for the prompt component of 3x10^53 erg and 1.6x10^52 erg for the afterglow; there is no evidence for a jet break in the afterglow up to six days following the burst.Comment: 15 pages, 9 figures, 4 in colour. Accepted for publication in MNRA