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Abstract Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.

Abstract Generalizing the quantum sine-Gordon and sausage models, we construct exact S-matrices for higher spin representations with quantum U q su 2 $$ {\mathcal{U}}_{\textrm{q}}\left({\mathfrak{su}}_2\right) $$ symmetry, which satisfy unitarity, crossing-symmetry and the Yang-Baxter equations with minimality assumption, i.e. without any unnecessary CDD factor. The deformation parameter q is related to a coupling constant. Based on these S-matrices, we derive the thermodynamic Bethe ansatz equations for q a root of unity in terms of a universal kernel where the nodes are connected by graphs of non-Dynkin type. We solve these equations numerically to find out Hagedorn-like singularity in the free energies at some critical scales and find a universality in the critical exponents, all near 0.5 for different values of the spin and the coupling constant.

The study explores intercultural competences in the field of international cooperation. The substantive research question was whether Italian operators who have gained experience abroad, think they have developed intercultural competences and what competences they think they possess. This study involved a total of 20 representatives of Non-Governmental Organisations (NGOs) from Lombardy (Italy), 16 operators working for NGOs in developing countries and 10 Italian international professionals from the UNDP and WHO agencies based in Geneva (Switzerland). In this empirical research project, a semi-structured interview was administered to NGO leaders, a questionnaire to NGO co-operators and UN international operators and a narrative interview to the latter. Qualitative methods of textual analysis were used. The author has created a dynamic model of intercultural competences consisting of fifteen recurrent competences. In this article, the author presents her model and how to assess intercultural competences. The empirical study involving professionals of Italian nationality. The topic of intercultural competences raises a substantial question about their deep, inner workings in the individual. Key issues for future developments in intercultural competences training are made explicit.

BackgroundCommunity health centers (CHCs) provide comprehensive primary and preventive care to medically underserved, low-income, and racially/ethnically diverse populations. CHCs also offer enabling services, non-clinical assistance to reduce barriers to healthcare due to unmet social and material needs, to improve access to healthcare and reduce health disparities. For patients with modifiable cardiometabolic risk factors, including obesity, hypertension, and diabetes, enabling services may provide additional support to improve disease management. However, little is known about the relationship between enabling services and healthcare accessibility and utilization among patients with cardiometabolic risk factors.MethodsThis study uses data from the 2014 Health Center Patient Survey to examine the relationship between enabling services use and delayed/foregone care, routine check-ups, and emergency room visits, among adult community health center patients in the United States with cardiometabolic risk factors (N = 2358). Outcomes of enabling services users were compared to nonusers using doubly robust propensity score matching methods and generalized linear regression models.ResultsOverall, enabling service users were 15.4 percentage points less likely to report delayed/foregone care and 29.4 percentage points more likely to report routine check-ups than nonusers. Enabling service users who lived in urban areas, younger and middle-aged adults, and those with two cardiometabolic risk factors were also less likely to report delayed/foregone care and/or more likely to report routine check-ups in comparison with nonusers. However, among adults with three or more cardiometabolic risk factors, enabling services use was associated with a 41.3 percentage point increase in emergency room visits and a 7.6 percentage point decrease in routine check-ups.ConclusionsThe findings highlight the value in utilizing enabling services to improve timeliness and receipt of care among CHC patients with heightened cardiometabolic risk. There is a need for targeting high-risk populations with additional enabling services to support management of multiple chronic conditions.

One of the sources of sustainable energy with great, still untapped potential is wind power. One way to harness such potential is to develop technology for offshore use, more specifically at high depths with floating turbines. It is always critical that their structural designs guarantee that their natural frequencies of vibration do not match the frequencies of the most important oscillatory loads to which they will be subjected. This avoids resonance and its excessive undesired oscillatory responses. Based on that, a 3D finite element model of a 15 MW semi-submersible floating offshore wind turbine was developed in the commercial software ANSYS Mechanical ® to study its dynamic behavior and contribute to the in-depth analysis of structural modeling of FOWTs. A tower and floating platform were individually modeled and coupled together. The natural frequencies and modes of vibration of the coupled system and of its components were obtained by modal analysis, not only to verify the resonance, but also to investigate the determinant factors affecting such behaviors, which are not extensively discussed in literature. It was found that there is strong coupling between the components and that the tower affects the system as a result of its stiffness, and the floater as a result of its rotational inertia. The platform’s inertia comes mainly from the ballast and the effects of added mass, which was considered to be a literal increase in mass and was modeled in two manners: first, it was approximately calculated and distributed along the submerged flexible platform members and then as a nodal inertial element with the floater being considered as a rigid body. The second approach allowed an iterative analysis for non-zero frequencies of vibration, which showed that a first approximation with an infinite period is sufficiently accurate. Furthermore, the effects of the mooring lines was studied based on a linear model, which showed that they do not affect the boundary conditions at the bottom of the tower in a significant way.

Eucalyptus-based glued laminated timber (glulam) was produced to determine the feasibility of a non-destructive method (drilling resistance) to predict the properties of structural elements and add value to lower-quality hardwood species. Glulam was manufactured with formaldehyde (Resorcinol), reference condition, and bio-based (Castor oil-based) adhesives in two assembly schemes, the core composed either of two continuous lamellae each 105 cm long, or of two formed by the juxtaposition of shorter boards (35 and 55 cm). The shear strength of the glue line (fv0), modulus of elasticity (Ec90), and strength (fc90) in compression perpendicular to the grain; delamination (DL); and main and extended glue line thicknesses were evaluated. The Resistograph equipment was used to perform the perforation perpendicular to the glue line (samples extracted from the glulam elements) to correlate the properties. The results of this research demonstrate that the scheme of the boards had little effect on the physical and mechanical properties evaluated (except the main glue line and delamination), and the drilling resistance (DR) presents a significant correlation with practically all properties evaluated (variations in density values and other properties are explained by variations in DR values), making it possible to estimate Ec90 and fc90 with desired precision (R2adj ≈ 80%). This highlights the feasibility of using this methodology in the quality control of glulam elements. It is concluded that regardless of the adhesive, elements comprising a 105 cm-length core and external lamellae (T1 and control) are indicated for external use, presenting low delamination. Short-length central lamellae adhesively glued with PUR (T2) are not recommended for external applications due to their susceptibility to delamination. However, T2 is indicated for internal environments due to its low production cost. This study also proved the efficiency of using models based on drilling resistance to estimate wood density and its resistance to compression perpendicular to the fiber.

Characterization of different organic wastes is essential to reveal alternative nutrient sources useful for agriculture. The objective of this work was to characterize a variety of organic wastes generated in the Brazilian Amazon in order to identify nutrient sources for potential use as organic fertilizers. Samples of nine different organic wastes from agricultural, livestock and forestry activities were collected in the state of Pará, Amazon region, Brazil. These samples were characterized using reference methods for analyses of organic fertilizers. Palm oil mill boiler ash was highly concentrated in P, K, Ca, and Mg and also highly alkaline, being considered a promising material for use as fertilizer and lime in acid soils. Palm oil mill decanter cake was the best N source; it also contained relevant amounts of K, S, and Zn. Cattle manure was more concentrated in N and oil palm empty fruit bunch in K. Residual eucalyptus charcoal was high in Ca but also in Na and Al. Oil palm fruit fiber, oil palm fruit shell, wood sawdust of the pile top, and wood sawdust of the pile slope were consistently poor in nutrients. All wastes presented low concentrations of As, Ba, Cd, Cr, Hg, Pb, and Se. This study identified organic wastes differing in prevalent nutrients for potential use as organic fertilizers. Such a difference could be explored in further studies by combining two or more wastes with complementary prevalent nutrients in order to better meet the nutritional requirements of different crops in the Brazilian Amazon.

This presentation reviews images of electron micrographs from various skeletal muscles identifying a consistent association of diydropyridine receptors (DHPR) tetrads with alternate ryanodine receptors. Imaging of the junctional gap in triads from various sources provide direct evidence for the association of four diydropyridine receptors (DHPRs), clustered into tetrads, with alternate ryanodine receptors (RyRs). It is not clear whether firing of all four components of a tetrad is necessary to fully activate the opening of the RyR channel.

Diante ao preocupante cenáriomundial sobre a obesidade e a importância de intervenções multiprofissionais para mudança no estilo de vida da população com obesidade. O Objetivo foi analisar os efeitos de um programa multiprofissional para tratamento da obesidade com treinamento aquático, nos parâmetros bioquímicos, composição corporal e da aptidão física de adultos obesidade severa. O estudo foi conduzido por equipe multiprofissional com profissionais de Educação Física, Nutrição, Psicologia e Medicina, durante 24 semanas, com 16 indivíduos classificados com obesidade severa (IMC > 40 kg/m2). As Intervenções do programa proposto no estudo foram realizadas através treinamento aquático de exercícios aeróbicos associados com a orientação nutricional e psicológica. Foi analisada diminuição significativa no índice de Proteína C Reativa (mg/L) (p=0,0439); no percentual de gordura (%), ao final das 24 semanas do programa de tratamento (p=0,0136), também houve aumento significativo na força de pressão manual (kg) com 16 semanas (p=0,0006) e 24 semanas (p=0,0014). Este estudo apresentou resultados significativos na melhora dos parâmetros bioquímicos, composição corporal e da aptidão física em adultos com obesidade severa, justificando o quanto programas de tratamentos que visam a mudanças nos hábitos alimentares e estilo de vida são de grande importância para a saúde pública

BackgroundUnder emergency coronavirus disease 2019 pandemic regulations, Medicare granted temporary payment parity with in-person visits for audio-only (telephone) telemedicine visits. This policy was designed to expand telemedicine to patients without camera-equipped devices and broadband internet. However, audio-only telemedicine use has been substantial.ObjectiveThe aim of this study was to explore whether the rate of audio-only telemedicine during the pandemic is related to patient access to technology or provider behavior.DesignCross-sectional analysis of the Summer and Fall 2020 Medicare Current Beneficiary Survey coronavirus disease 2019 supplements, using multivariable logistic models and accounting for complex survey design.SubjectsA total of 3375 participants in the summer survey and 2633 participants in the fall 2020 were offered a telemedicine visit to replace a scheduled in-person visit by their usual care provider.MeasuresWe compared beneficiaries who were exclusively offered audio-only telemedicine to beneficiaries who were offered video telemedicine or both audio and video.ResultsWe found that among Medicare beneficiaries who were offered telemedicine to replace a scheduled in-person appointment, ~35% were exclusively offered audio-only. 65.8% of beneficiaries exclusively offered audio-only reported having a smartphone/tablet and home internet. After controlling for personal access to technology, Hispanic [adjusted odds ratio (AOR)=2.09, P

Valorisation of cultural heritage is a priority of international community, and the creation of 3D models is considered almost a mandatory requirement to any conservation activity. Geomatics has given its contribution to this purpose offering its competences and experiences in surveying. Methods and tools have progressively improved offering more realistic, accurate, and reliable products; among the most interesting systems currently available, there is the handheld mobile mapping Leica BLK2GO technology. The characteristics of this system are particularly useful when traditional methods are unfeasible due to accessibility problem, narrowness spaces and time constraints. Nevertheless, the system, as any new technology, needs to be tested in order to verify its capability to describe the world in a correct and reliable way; moreover, it is interesting to understand if established data classification procedures are still effective for SLAM (Simultaneous Localization and Mapping) data. The paper is framed in this context and illustrates the survey of an ancient crypt, located in Pavia (Italy), that is object of a preservation project. The characteristics of the monument and the acquisition strategies are described. For data classification three different Machine Learning approaches are test: Support Vector Machine (SVM), Decision Tree (DT) and Random Forest (RF). Seven architectural elements are considered: pavement, columns, half pilasters with structural function, walls, capitals, arches, and vaults. The analysis shows as Leica BLK2GO data owns all the characteristics feasible to produce useful point cloud; data classification performs well (with the exceptions of SVM) with higher accuracy, of about 90%, reached using RF.

Abstract Background Healthcare disparities are an issue in the management of Congenital Heart Defects (CHD) in children. Although universal insurance may mitigate racial or socioeconomic status (SES) disparities in CHD care, prior studies have not examined these effects in the use of High-Quality Hospitals (HQH) for inpatient pediatric CHD care in the Military Healthcare System (MHS). To assess for racial and SES disparities in inpatient pediatric CHD care that may persist despite universal insurance coverage, we performed a cross-sectional study of the HQH use for children treated for CHD in the TRICARE system, a universal healthcare system for the U.S. Department of Defense. In the present work we evaluated for the presence of disparities, like those seen in the civilian U.S. healthcare system, among military ranks (SES surrogate) and races and ethnicities in HQH use for pediatric inpatient admissions for CHD care within a universal healthcare system (MHS). Methods We conducted a cross-sectional study using claims data from the U.S. MHS Data Repository from 2016 to 2020. We identified 11,748 beneficiaries aged 0 to 17 years who had an inpatient admission for CHD care from 2016 to 2020. The outcome variable was a dichotomous indicator for HQH utilization. In the sample, 42 hospitals were designated as HQH. Of the population, 82.9% did not use an HQH at any point for CHD care and 17.1% used an HQH at some point for CHD care. The primary predictor variables were race and sponsor rank. Military rank has been used as an indicator of SES status. Patient demographic information at the time of index admission post initial CHD diagnosis (age, gender, sponsor marital status, insurance type, sponsor service branch, proximity to HQH based on patient zip code centroid, and provider region) and clinical information (complexity of CHD, common comorbid conditions, genetic syndromes, and prematurity) were used as covariates in multivariable logistic regression analysis. Results After controlling for demographic and clinical factors including age, gender, sponsor marital status, insurance type, sponsor service branch, proximity to HQH based on patient zip code centroid, provider region, complexity of CHD, common comorbid conditions, genetic syndromes, and prematurity, we did not find disparities in HQH use for inpatient pediatric CHD care based upon military rank. After controlling for demographic and clinical factors, lower SES (Other rank) was less likely to use an HQH for inpatient pediatric CHD care; OR of 0.47 (95% CI of 0.31 to 0.73). Conclusions We found that for inpatient pediatric CHD care in the universally insured TRICARE system, historically reported racial disparities in care were mitigated, suggesting that this population benefitted from expanded access to care. Despite universal coverage, SES disparities persisted in the civilian care setting, suggesting that universal insurance alone cannot sufficiently address differences in SES disparities in CHD care. Future studies are needed to address the pervasiveness of SES disparities and potential interventions to mitigate these disparities such as a more comprehensive patient travel program.

Introduction Surgical site infections still remain a major public health challenge and have become an increasing universal risk, especially for the implantation of orthopaedic devices.Unfortunately, the discovery and increasingly widespread use (especially the misuse) of antibiotics have led to the rapid appearance of antibiotic-resistant strains today; more and more infections are caused by microorganisms that fail to respond to conventional treatments.Oxygen-ozone therapy has been extensively used and studied for decades across various potential medical applications and has provided consistent effects with minimal side effects.This study aims to determine the superiority of oxygen-ozone therapy in combination with oral antibiotic therapy in patients with wound infections after an orthopaedic device implantation when compared with antibiotic therapy alone.Methods and analysis This is an open-label, multicentre, randomised, parallel-group study that aims to assess the efficacy and safety of oxygen-ozone therapy in combination with oral antibiotic therapy to treat infections in patients (male or female aged ≥18 years) having undergone surgery for the implant of an orthopaedic device. Patients must have at least one (but no more than three) postoperative wounds in the site of surgery (ulcers, eschars and sores) and at least one symptom (pain, burning, redness and malodour) and at least one sign (erythema, local warmth, swelling and purulent secretion) of infection of at least moderate intensity (score ≥2) in the target lesion at the screening visit (patients with wounds without signs of localised infection or with undermining wounds will be excluded).Patients (n=186) will be recruited from five Italian hospitals and studied for 7 weeks. All will be assigned to one of the two treatment groups according to a web-based, centralised randomisation procedure and placed into either the (1) intervention: oxygen-ozone therapy 2–3 times a week for 6 weeks (for a maximum of 15 sessions) simultaneously with an appropriate oral antibiotic therapy prescribed at baseline or (2) control: oral antibiotic therapy prescribed at baseline.The primary outcome is the efficacy and superiority of the treatment (ozone and oral antibiotic therapies); secondary outcomes include the resolution of signs and symptoms, modifications in lesion size and the treatment’s safety and tolerability.Ethics and dissemination This study has been reviewed and approved by the responsible Independent Ethics Committee (IEC) of COMITATO ETICO CAMPANIA NORD, located at ‘Azienda Ospedaliera San Giuseppe Moscati di Avellino’.After completion of the study, the project coordinator will prepare a draft manuscript containing the final results of the study on the basis of the statistical analysis. The manuscript will be derived by the co-authors for comments, and after revision, it will be sent to a major scientific journal. Findings will be disseminated via online and print media, events and peer-reviewed journals.Trial registration number NCT04787575.

Spatial and temporal variations can influence the abundance and biology of parasite species and even the transmission process, as well as the diet, reproduction and distribution of hosts. We studied the influence of seasonality on the diet and endoparasites of the lizard Strobilurus torquatus. The lizards were collected during a period of one year, in the Engenho Gargaú Private Reserve of Natural Heritage, located in the municipality of Santa Rita, in the state of Paraíba, Northeast Brazil. Thirty-three lizards were analysed, of which 30 were parasitised (overall prevalence of 90%) with the helminths Physaloptera lutzi (prevalence of 69.6%), Spauligodon loboi (51.5%), Strongyluris oscari (15.1%) and Haplometroides odhneri (3.0%). Our analysis showed that endoparasite abundance was influenced by host body size (R2m: 0.95; R2c: 0.95; Z-value: 11.521; P < 0.0001). Host sex also influenced endoparasite abundance, where males were parasitised more than females (Z-value: 6.260; P < 0.001). When comparing the two seasons (dry and rainy), we observed that the greatest endoparasites abundance occurred during the rainy season (Z- value: -2.422; P < 0.05). Regarding the lizards’ diet, we observed a high niche overlap (overlap index of 0.999), which indicates that males and females of S. torquatus consumed practically the same prey during the analysed period. The life cycle of the endoparasites found in S. torquatus was linked to seasonal variation, and the behavioural and physiological differences between sexes may have influenced the variations in endoparasite abundance.

The purpose of this study is to examine the geographical patterns of adjuvant hormonal therapy adherence and persistence and the associated factors in insured Texan women aged 18–64 with early breast cancer. A retrospective cohort study was conducted using 5-year claims data for the population insured by the Blue Cross Blue Shield of Texas (BCBSTX). Women diagnosed with early breast cancer who were taking tamoxifen or aromatase inhibitors (AIs) for adjuvant hormonal therapy with at least one prescription claim were identified. Adherence to adjuvant hormonal therapy and persistence with adjuvant hormonal therapy were calculated as outcome measures. Women without a gap between two consecutively dispensed prescriptions of at least 90 days were considered to be persistently taking the medications. Patient-level multivariate logistic regression models with repeated regional-level adjustments and a Cox proportional hazards model with mixed effects were used to determine the geographical variations and patient-, provider-, and area-level factors that were associated with adjuvant hormonal therapy adherence and persistence. Of the 938 women in the cohort, 627 (66.8%) initiated adjuvant hormonal therapy. Most of the smaller HRRs have significantly higher or lower rates of treatment adherence and persistence rates relative to the median regions. The use of AHT varies substantially from one geographical area to another, especially for adherence, with an approximately two-fold difference between the lowest and highest areas, and area-level factors were found to be significantly associated with the compliance of AHT. There are geographical variations in AHT adherence and persistence in Texas. Patient-level and area-level factors have significant associations explaining these patterns.

In vivo compatible reactions have a broad range of possible applications in chemical biology and the pharmaceutical sciences. Here we report tetrazines that can be removed by exposure to isonitriles under very mild conditions. Tetrazylmethyl derivatives are easily accessible protecting groups for amines and phenols. The isonitrile-induced removal is rapid and near-quantitative. Intriguingly, the deprotection is especially effective with (trimethylsilyl)methyl isocyanide, and serum albumin can catalyze the elimination under physiological conditions. NMR and computational studies revealed that an imine-tautomerization step is often rate limiting, and the unexpected cleavage of the Si-C bond accelerates this step in the case with (trimethylsilyl)methyl isocyanide. Tetrazylmethyl-removal is compatible with use on biomacromolecules, in cellular environments, and in living organisms as demonstrated by cytotoxicity experiments and fluorophore-release studies on proteins and in zebrafish embryos. By combining tetrazylmethyl derivatives with previously reported tetrazine-responsive 3-isocyanopropyl groups, it was possible to liberate two fluorophores in vertebrates from a single bioorthogonal reaction. This chemistry will open new opportunities towards applications involving multiplexed release schemes and is a valuable asset to the growing toolbox of bioorthogonal dissociative reactions.

Abstract Background Comparative prospective data regarding different radiosurgery (SRS) modalities for treating brain metastases (BMs) from solid tumors are not available. To investigate with a single institute phase III randomized trial whether SRS executed with linac (Arm-B) is superior to a dedicated multi-source gamma-ray stereotactic platform (Arm-A). Methods Adults patients with 1–4 BMs from solid tumors up to 30 mm in maximum diameter were randomly assigned to arms A and B. The primary endpoint was cumulative incidence of symptomatic (grade 2–3) radionecrosis (CIRN). Secondary endpoints were local progression cumulative incidence (CILP), distant brain failure, disease-free survival (DFS), and overall survival (OS). Results A total of 251 patients were randomly assigned to Arm-A (121) or Arm-B (130). The 1-year RN cumulative incidence was 6.7% in whole cohort, 3.8% (95% CI 1.9–7.4%) in Arm-B, and 9.3% (95% CI 6.2–13.8%) in the Arm-A (p = 0.43). CIRN was influenced by target volume irradiated only for the Arm-A (p <

Thermo-mechanical densification modifies wood to produce a more dense and resistant lignocellulosic material and may degrade extractives that contribute to the increased susceptibility of wood to attack by xylophagous organisms. This study evaluated the efficiency of tannin extracts of Acacia mearnsii in the treatment of thermo-mechanical densified pine wood in relation to physical, mechanical, and biological resistance (Cryptotermes brevis) properties. Pinus elliottii samples were pretreated with oxalic acid in a Parr reactor, then treated by diffusion in tannin solutions at concentrations 5, 10, and 15%, and finally hot pressed. The apparent density of the modified wood was 87.8% greater than that of the in natura wood (control) with tannins at 15%. The mechanical strength increased, especially the parallel compressive strength, which had an average increase of 169% for the wood with tannins at 10 and 15%, compared with the in natura wood. There was an increase in termite mortality and a reduction in damage for the modified wood treated with 15% tannins, obtaining the best results in mechanical and biological resistance and for the physical parameters. Thermal densification pine wood and preserved with tannin extractives proved to be a potential alternative as a high performance material.

Alfredo Chetta,1 Nicola Facciolongo,2 Cosimo Franco,3 Laura Franzini,4 Alessio Piraino,4 Carmelina Rossi4 1Clinica Pneumologica, Università di Parma, Parma, Italy; 2UOC Pneumologia, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; 3UOC Pneumologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy; 4Chiesi Italia SpA, Medical Affairs, Parma, ItalyCorrespondence: Alfredo Chetta, Tel +39 0521.703478, Email alfredoantonio.chetta@unipr.itAbstract: In recent years, the perspective of management of respiratory disease has been gradually changing in light of the increasing evidence of small airways as the major site of airflow obstruction contributing to the development of both COPD and asthma already in early stages of disease. First and foremost, the evidence is redefining disease severity, identifying small airways disease phenotypes and early signs of disease, and revising prevalence and overall epidemiological data as well. Much effort has been put toward the instrumental assessment of small airways’ involvement and early detection. Several clinical trials have evaluated the advantage of extra-fine formulations which can best target the small airways in uncontrolled asthma and severe COPD. Here, we briefly present a practical overview of the role of the small airways in disease, the most appropriate diagnostic methods for quantifying their impairment, and provide some insight into the costs of respiratory management in Italy, especially in sub-optimally controlled disease.Keywords: asthma, chronic obstructive pulmonary disease, small airways, impulse oscillometry, cost, extrafine particles

Background. Ozone is an allotrope of oxygen whose use in medicine has rapidly grown in recent years. Ozonated blood allows for the use of ozone in a safe modality, as plasma and blood cells are endowed with an antioxidant system able to quench ozone’s pro-oxidant property and to elicit the Nrf2/Kwap1/ARE pathway. Methods. We present two clinical studies, a case-series (six patients) observational study adopting ozone as a major autohemotherapy and topical ozone to address infected post-surgical wounds with multi-drug resistant bacteria and an observational study (250 patients) using ozonated blood for treating knee osteoarthritis. Results. Ozonated blood via major autohemotherapy reduced the extent of infections in wounds, reduced the inflammatory biomarkers by more than 75% and improved patients’ QoL, whereas ozonated blood via minor autohemotherapy improved significantly (p < 0.001) WOMAC and Lequesne’s parameters in knee osteoarthritis. Conclusions. The models described, i.e., ozone autohemotherapy in wound antimicrobial treatment and ozonated blood in knee osteoarthrosis, following our protocols, share the outstanding ability of ozone to modulate the innate immune response and address bacterial clearance as well as inflammation and pain.

The isocyano group is a structurally compact bioorthogonal functional group that reacts with tetrazines under physiological conditions. Now it is shown that bulky tetrazine substituents accelerate this cycloaddition. Computational studies suggest that dispersion forces between the isocyano group and the tetrazine substituents in the transition state contribute to the atypical structure-activity relationship. Stable asymmetric tetrazines that react with isonitriles at rate constants as high as 57 L mol-1  s-1 were accessible by combining bulky and electron-withdrawing substituents. Sterically encumbered tetrazines react selectively with isonitriles in the presence of strained alkenes/alkynes, which allows for the orthogonal labeling of three proteins. The established principles will open new opportunities for developing tetrazine reactants with improved characteristics for diverse labeling and release applications with isonitriles.