From triggers to asthma: a narrative review on epithelium dysfunction.

Summary: It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

Systemic treatment in advanced phyllodes tumor of the breast: a multi-institutional European retrospective case-series analyses.

BACKGROUND: We aimed at investigating outcome of systemic treatments in advanced breast PT. METHODS: All cases of advanced breast PT treated with systemic treatments from 1999 to 2019, in one of the referral sarcoma centers involved in the study, were retrospectively reviewed. RESULTS: 56 female patients were identified. Median age was 52 (range of 25-76) years. Patients received a median number of 2 systemic treatments (range of 1-4). Best responses according to RECIST were 1 (3.7%) CR, 11 (40.7%) PR, 6 (22.2%) SD, 9 (33.3%) PD with anthracyclines plus ifosfamide (AI); 2 (16.7%) PR, 4 (33.3%) SD, 6 (50.0%) PD with anthracycline alone; 3 (18.8%) PR, 4 (25.0%) SD, 9 (56.3%) PD with high-dose ifosfamide given as a continuous infusion (HD-IFX); 3 (20.0%) SD, 12 (80.0%) PD with a gemcitabine-based regimen (with 2 patients not evaluable); 1 (8.3%) PR, 2 (16.7%) SD, 9 (75.0%) PD with trabectedin (with 1 patient not evaluable); 1 (16.7%) PR, 1 (16.7%) SD, 4 (66.7%) PD with tyrosine-kinase inhibitors (TKI). The median PFS were 5.7 (IQR 2.5-9.1) months with AI; 3.2 (IQR 2.2-5.0) months with anthracycline alone; 3.4 (IQR 1.4-6.7) months with HD-IFX; 2.1 (IQR 1.4-5.2) months with gemcitabine-based chemotherapy; 1.8 (IQR 0.7-6.6) months with trabectedin; 3.4 (IQR 3.1-3.8) months with TKI. With a median follow-up of 35.3 (IQR 17.6-66.9) months, OS from the start of first-line systemic treatment was 15.2 (IQR 7.6-39.6) months. CONCLUSION: In this series of advanced PT (to our knowledge, the largest reported so far), AI was associated with a high rate of responses, however, with a median PFS of 5.7 months. Other systemic treatments were poorly active.

An objective, markerless videosystem for staging facial palsy.

PURPOSE: To propose a new objective, video recording method for the classification of unilateral peripheral facial palsy (UPFP) that relies on mathematical algorithms allowing the software to recognize numerical points on the two sides of the face surface that would be indicative of facial nerve impairment without positioning of markers on the face. METHODS: Patients with UPFP of different House-Brackmann (HB) degrees ranging from II to V were evaluated after video recording during two selected facial movements (forehead frowning and smiling) using a software trained to recognize the face points as numbers. Numerical parameters in millimeters were obtained as indicative values of the shifting of the face points, of the shift differences of the two face sides and the shifting ratio between the healthy (denominator) and the affected side (numerator), i.e., the asymmetry index for the two movements. RESULTS: For each HB grade, specific asymmetry index ranges were identified with a positive correlation for shift differences and negative correlation for asymmetry indexes. CONCLUSIONS: The use of the present objective system enabled the identification of numerical ranges of asymmetry between the healthy and the affected side that were consistent with the outcome from the subjective methods currently in use.

Natural history of SARS-CoV-2 infection in healthcare workers in Northern Italy.

At present, the time-frame used for the quarantine of individuals with coronavirus disease 2019 (COVID-19) is the entire duration of symptoms plus 14 days after symptom recovery; however, no data have been reported specifically for healthcare workers (HCWs). In the study population of 142 HCWs with COVID-19, the mean time for viral clearance was 31.8 days. Asymptomatic subjects cleared the virus more quickly than symptomatic subjects (22 vs 34.2 days; P<0.0001). The presence of fever at the time of diagnosis was associated with a longer time to viral clearance (relative risk 11.45, 95% confidence interval 8.66-14.25; P<0.0001). These findings may have a significant impact on healthcare strategies for the future management of the COVID-19 pandemic.

Effect of different music genres on gait patterns in Parkinson's disease.

The timing and size of repetitive, internally generated, automatic sequences of movements are particularly affected in Parkinson's disease. The most evident consequence of this deficit is the alteration of gait patterns, with a loss of rhythmicity, shorter steps, slower walking, and trunk instability. Several studies have highlighted a potential benefit of listening to music on the normalization of walking patterns. However, most of these studies investigated the effect of a single specific music. We hypothesized that different musical genres may induce different modifications of spatiotemporal parameters and trunk oscillations during walking. In this study, we enrolled healthy young subjects, healthy elderly, and patients with Parkinson's disease. They were asked to walk listening, by a wireless headset, one of six different music tracks (related to four different musical genres) while wearing an inertial measurement unit at pelvis level used to assess their walking patterns. The main effect of music tracks resulted statistically significant in all the gait parameters (p < 0.05), but for symmetry of lower trunk movements. This effect was independent by group. The only significant interaction between music and group, in fact, was found for pelvis obliquity range of motion (p = 0.019). Post hoc analyses showed as classical music reduced speed and trunk tilting (p < 0.01), whereas the range of pelvic obliquity movements in frontal plane were increased by rock, motivational, and heavy metal songs (p < 0.015). In conclusion, the gait patterns were altered by listening music depending by the musical genre, and these adaptations occurred similarly among the three groups, including patients with Parkinson's disease.

3D MRI segmentation and 3D circumferential resection margin evaluation for a standard rectal cancer assessment.

AIM: Recent studies focused on rectal cancer suggested that a 3D imaging segmentation obtained from MRI data could contribute in the definition of the circumferential resection margin (CRM) and in the assessment of the tumor regression following neo-adjuvant treatments. Here, we propose a method for defining and visualizing the circumferential margins using 3D MRI segmentation; this methodology was tested in a clinical study comparing 3D CRM assessment vs standard MRI imaging. PATIENTS AND METHODS: MRI scans performed before neo-adjuvant treatments were selected and reviewed. 3D mesorectal/tumor segmentations were obtained using Digital Imaging and COmmunications in Medicine (DICOM) data; CRMs were calculated using 3D volumes plus a color scale for the closest distances. RESULTS: 3D reconstructions were possible in all selected cases and 3D images implemented by the color scale were positive for immediate CRM visualization. Statistical analyses comparing standard radiology disclosed that the degree of consistency, the reliability of ratings, the correlation and precision were optimal considering the overall cases, but lower in the CRM>0 mm sub-group. CONCLUSIONS: This new method is not inferior comparing standard radiology; moreover, the imaging segmentation we obtained was highly promising and could be helpful in defining a standard CRM measurement, thus it could improve clinical practice.

A topological look at human trabecular bone tissue.

Bone quality is affected by trabecular architecture at microscopic level. Various abnormalities of bone tissue lead to altered strength and to an increased susceptibility to fracture, such as Osteoporosis and Osteoarthritis, two major health burdens of our society. These are two complex musculoskeletal diseases that mainly concern bone tissue. In the last twenty years, there has been a growing interest in finding an appropriate topological model for the micro-architecture of trabecular bone tissue. In particular, we prove that these models involve general topological spaces. The appropriate notion to deal with is that of CW-complex.

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target.

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z > 1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at [Formula: see text] and [Formula: see text] with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

Note: Experimental study on feasibility of a flexural traveling wave piezoelectric device for biomedical micro-electromechanical system.

The aim of this paper is to experimentally show that polyvinylidene fluoride biaxially oriented in bimorph configuration is a suitable flexural traveling wave device. Piezoelectric ceramic is promising, however the lack biocompatibility is the main drawback for biomedical micro-electromechanical system. A prototype of 20 mm diameter was designed, constructed, and tested via an optical method. A first investigation was performed on two standing waves which were excited to generate the traveling wave. The findings of amplitude and phase have revealed a B31 vibration mode at 7.2 kHz and a maximum amplitude of roughly 40 nm. The flexural traveling wave was confirmed experimentally.

Measurement of charged particle yields from PMMA irradiated by a 220 MeV/u (12)C beam.

The radiation used in hadrontherapy treatments interacts with the patient body producing secondary particles, either neutral or charged, that can be used for dose and Bragg peak monitoring and to provide a fast feedback on the treatment plans. Recent results obtained from the authors on simplified setups (mono-energetic primary beams interacting with homogeneous tissue-like target) have already indicated the correlation that exists between the flux of these secondaries coming from the target (e.g. protons and photons) and the position of the primary beam Bragg peak. In this paper, the measurements of charged particle fluxes produced by the interaction of a 220 MeV/u carbon ion beam at GSI, Darmstadt, with a polymethyl methacrylate target are reported. The emission region of protons (p), deuterons (d) and tritons (t) has been characterized using a drift chamber while the particle time-of-flight, used to compute the kinetic energy spectra, was measured with a LYSO scintillator. The energy released in the LYSO crystal was used for particle identification purposes. The measurements were repeated with the setup at 60° and 90° with respect to the primary beam direction. The accuracy on the fragments emission profile reconstruction and its relationship with the Bragg peak position have been studied. Based on the acquired experimental evidence, a method to monitor the dose profile and the position of the Bragg peak inside the target is proposed.

Note: Comparative experimental studies on the performance of 2-2 piezocomposite for medical ultrasound transducers.

The paper reports the experimental investigation of the behavior of 2-2 Lead Zirconate Titanate (PZT)-polymer composite transducers array for clinical ultrasound equipments. Several 2-2 plate composites having the same dicing pitch of 0.11 mm and different volume fractions were manufactured and investigated. Measurements were performed through different techniques such as electrical impedance, pulse-echo, and Laser Doppler Vibrometer. With the last one, maps of the surface displacement were presented relative to thickness mode and first lateral mode resonance frequencies. The transducers with volume fractions of the 40% resulted markedly inefficient, whereas the largest bandwidth and best band shape were achieved by the 50%.

Preliminary study of early histomorphometric changes in hepatic steatosis.

The first endpoint of this study was to find new markers that document the progression of hepatic steatosis through quantitative histomorphometric analysis in the absence of hemodynamic changes. The second endpoint was to start building a mathematical database to help to achieve a score in the future. For this study we enrolled 130 random patients, including 10 with normal histology despite suspected disease, 70 positive for steatosis, 20 affected by nonalcoholic steato hepatitis, and 30 with hepatitis virus C or B-related cirrhosis. One hundred thirty images were analyzed for a total of 1,320 sinusoids. Each image was processed with a custom program written with the use of the Vision toolbox of the Labview platform, following a semiautomated procedure. The mean sinusoidal areas (SAs) and percentage fractions of parenchymal area occupied by sinusoids (SA/PA) were subdivided into 3 groups. Finally, we analyzed the form of sinusoids, approximating them to an ellipse, to be able to define the relationship between the 2 axes with the aim of proposing a parameter, "local hydraulic resistance" (LHR), that was proportional to the resistance to blood flow within the bounds of the histologic specimen. Among the images, we observed a difference in the size of SAs among the 3 groups of patients, namely, normal, steatotic of different stages, and cirrhotic patients. In fact, there was evidence of a reducted SA when steatosis was <30%, with an average value of 0.0032 mm(2), patients with steatosis of 30%-50% showed an average SA of 0.0024 mm(2), and there was a further reduction among subjects with steatosis grades >50% (mean 0.0017 mm(2)). The LHR value showed that the morphometric parameter SA/PA could be quantitatively interpreted also as a functional impairment relative to the increased resistance opposing blood flow in pathologic conditions.

Environmental effects on school age child psychomotricity.

AIM: This study had the following aims: to verify whether children living in different environmental areas present a different development degree of the functional prerequisites of psychomotricity; to test whether a targeted psychomotricity education program could favourably modify the potential differences which may be observed; to investigate the relationship, if any, between the anthropometric differences and the functional prerequisites of psychomotricity. METHODS: One hundred and sixty-five Italian children, 83 males and 82 females, 6-7 years old were enrolled in this study. Based on the provenance area, the children were subdivided into two groups: the urban one (N=85) and the rural one (N=80). Both groups underwent an initial psychomotor assessment including standardised psychomotor tests aimed at evidencing the general dynamic coordination ability and the static and dynamic balance capacity of every child. RESULTS: The findings of this research point out that children living in an urban setting selectively showed a lower degree of balance development, if compared to children living in rural areas; a targeted psychomotor education program favourably modified the differences in the balance development between the two examined groups, up to their disappearance. In the urban group the body mass index had a trend towards a negative relationship with balance development. CONCLUSION: Children grown up in an urban environment showed a delay in balance development, if compared to children of the same age grown up in rural areas. This study also clearly proves that such a delay may be regained by means of a targeted psychomotor education program.

Peripheral CD4+ CD25+ Treg cell expansion in lung transplant recipients is not affected by calcineurin inhibitors.

CD4+CD25+ regulatory T (Treg) cells have been shown to play a role in allograft tolerance and their peripheral counts vary according to the degree of graft acceptance in lung transplant recipients (LTR). Recent studies demonstrate that certain drugs might modulate generation, expansion and activity of Treg cells. Aim of this study was to evaluate the effect of therapeutic regimens used in our institution on peripheral CD4+CD25(high)CD69- Treg cell numbers in a group of 51 LTR with stable clinical conditions. They were treated with standard immunosuppression: calcineurin inhibitor (CNI)+azathioprine (AZA)+steroids (n=28) or with CNI+mycophenolate mofetil (MMF)+steroids (n=11) or with CNI+steroids (n=12). These stable LTR were compared with age-matched healthy controls (n=35) and with 19 LTR who developed bronchiolitis obliterans syndrome (BOS) and were treated analogously. Stable LTR showed higher peripheral Treg cell counts with respect to age-matched healthy controls (59.9+/-31.8/mul versus 42.1+/-16.9/mul, respectively; p<0.05). This increase was detectable in all patients treated with CNI either in association with AZA or MMF. During these treatments a significant expansion of Treg cell counts was detectable during acute rejection (AR) episodes (86.03+/-26.6/mul during AR versus 36.34+/-7.6 before AR; p<0,05). Moreover, the development of BOS was associated to a significant decrease of Treg cell counts irrespective to the immunosuppressive regimen used. In conclusion, therapeutic regimens based on CNI seem to allow a certain degree of peripheral Treg cell expansion in stable LTR.

Molecular cloning and sequencing of the beta-isopropylmalate dehydrogenase gene from the cyanobacterium Spirulina platensis.

The gene for beta-isopropylmalate dehydrogenase (EC 1.1.1.85) of Spirulina platensis (leuB) was cloned from a lambda EMBL3 genomic library by heterologous hybridization using the Nostoc UCD 7801 leuB gene as a probe. The sequence of the entire leuB coding region was determined as well as 645 bp of 5' flanking region and 956 bp of 3' flanking region. DNA sequencing revealed an open reading frame of 1065 nucleotides capable of encoding a polypeptide of 355 amino acids. Homologies between the amino acid sequence deduced from the nucleotide sequence of the S. platensis leuB gene and the amino acid sequences published for corresponding proteins either from bacteria or yeasts are 45% or more. Northern hybridization analysis indicated that the S. platensis leuB gene is transcribed as a single monocistronic RNA of approximately 1200 bases.

Structural organization of pBC1, a cryptic plasmid from Bacillus coagulans.

The complete nucleotide sequence of the Bacillus coagulans plasmid pBC1 was determined. The sequence revealed an open reading frame encoding a polypeptide of 259 amino acids. This open reading frame shows sequence similarity to genes coding for replication-associated proteins in a group of gram-positive bacterial plasmids known to replicate via single-stranded intermediates. A region required for replication in cis, when the intact replicon is supplied in trans, was identified as well.

Melanocytic naevi: clinical features and correlation with the phenotype in healthy young males in Italy.

Six-hundred and fifteen young healthy Italian males were examined for the number, localization and clinical features of melanocytic naevi. The data were correlated with the phenotype and skin type of the subjects. Eighty-eight per cent had melanocytic naevi, 7% congenital naevi and 21.3% atypical naevi with a diameter greater than 5 mm and indistinct or irregular borders and were variable in colour. Of the sample only 2.43% had more than 30 naevi. Those subjects with blond or red hair, fair skin, blue or green eyes and with a skin type of I and II had higher numbers of naevi which were more often atypical than those subjects with dark hair, brown eyes and who were skin types III-V.

[Hepatic hemangiomatosis with congestive cardiac failure and development into a cholostatic hepatopathy]. / Emangiomatosi epatica con scompenso cardiaco congestizio ed evoluzione in epatopatia colostatica.

The authors describe a case of hepatic hemangiomathosis in a three months old infant with a clinical picture of multiple cutaneous hemangioma, epatomegaly and severe cardiac failure. The cardiac catheterization with selective angiography showed extensive communication between the mammary artery and the hepatic circulation with the presence of large bloody areas into the markedly enlarged liver. The medical treatment with digitalis, diuretics, and corticosteroids obtained rapid resolution of the cardiac failure and of the A-V fistula signs. A clinical picture of severe liver cholostatic disease developed few months later which was confirmed by histological examination. The subsequent course has been favorable with complete clinical resolution of the liver disease.

[Bronchopulmonary dysplasia in very low birth weight infants]. / La displasia bronco-polmonare nei nati di peso molto basso.

The reported incidence of Bronchopulmonary dysplasia (BPD) varies from 5% to 68%. The different criteria used to define BPD are responsable for these discrepancies: some Authors include only patients with a clinical and radiological picture that fits the stage IV, as originally described by Northway, others use a more liberal approach and include all patients with manifestations of chronic pulmonary disease. We observed BPD in 12 of 22 (54%) survivors infants of very low birth weight (mean 1115 gm) and gestational age (mean 29,2 weeks). The infants were all born between November 1979 and March 1981. According to Ehrenkranz et al., we classified the radiological findings as severe, moderate and mild. We believe that the etiology of BPD in very low birth weight infants is multifactorial. However, pulmonary oxygen toxicity and immaturity are the most important causes.