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Abstract Background The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. Methods A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). Results Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. Conclusion A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

WTe2 is a multifunctional quantum material exhibiting numerous emergent phases in which tuning of the carrier density plays an important role. Here, we demonstrate two nonmonotonic changes in the electronic structure of WTe2 upon in situ electron doping. The first phase transition is interpreted in terms of a shear displacement of the top WTe2 layer, which realizes a local crystal structure not normally found in bulk WTe2. The second phase transition is associated with stronger interactions between the dopant atoms and the host, both through hybridization and electric field. These results demonstrate that electron doping can drive structural and electronics changes in bulk WTe2 with implications for realizing nontrivial band-structure changes in heterointerfaces and devices.

Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme for the homeostasis and metabolism of intracellular folate. However, it is known that one of the commonly found MTHFR gene SNPs (A222V) causes a decrease in activity which decreases folate levels and increases the accumulation of homocysteine in the blood. The purpose of this study was to investigate the molecular dynamics of MTHFR wild-type protein and MTHFR A222V mutant protein in silico. After some preparations, the crystal structure of MTHFR with code 6FCX obtained from the Protein Data Bank was used as the input file for molecular dynamics (MD) simulations. YASARA-Structure was employed for performing 50 ns production run of MD simulations. The deviation of the root-mean-squared deviation value of the backbone atoms (∆RMSDBb) of MTHFR wild-type is consistently less than 2 Å from the beginning of the MD simulations production runs. On the other hand, there is a sudden spike of ∆RMSDBb of MTHFR A222V from 15.01 to 20.00 ns of 2.221 Å. According to the analysis of ∆RMSDBb, MTHFR wild-type protein is considered stable and the MTHFR A222V mutant protein is considered unstable which may lead to various clinical problems for the person possessing this mutation.

The autophagy process recycles dysfunctional cellular components and protein aggregates by sequestering them in autophagosomes directed to lysosomes for enzymatic degradation. A basal level of autophagy is essential for skeletal muscle maintenance. Increased autophagy occurs in several forms of muscular dystrophy and in the merosin-deficient congenital muscular dystrophy 1A mouse model (dy3k/dy3k) lacking the laminin-α2 chain. This pilot study aimed to compare autophagy marker expression and autophagosomes presence using light and electron microscopes and western blotting in diagnostic muscle biopsies from newborns affected by different congenital muscular myopathies and dystrophies. Morphological examination showed dystrophic muscle features, predominance of type 2A myofibers, accumulation of autophagosomes in the subsarcolemmal areas, increased number of autophagosomes overexpressing LC3b, Beclin-1 and ATG5, in the merosin-deficient newborn suggesting an increased autophagy. In Duchenne muscular dystrophy, nemaline myopathy, and spinal muscular atrophy the predominant accumulation of p62+ puncta rather suggests an autophagy impairment.

This study aims to analyse the evolution of match running performance in relation to the age distribution of professional soccer players using a large-scale analysis. An explorational-longitudinal and retrospective study was designed and a total of 36,883 individual match observations were collected on outfield players competing across four consecutive Spanish LaLiga seasons (from 2015/16 to 2018/19), using an optical tracking system (ChyronHego). Soccer players were divided into 3 age groups: young (18–24 years old), middleaged (25–30 years old), and seniors (31–41 years old). Relative total distance (TD/min), distance covered at 21–24 km· h−1 (HIRD/min), and > 24 km· h−1 per minute (VHIRD/min) were analysed; also, the number of efforts at 21–24 km·h−1 (Sp21) and > 24 km·h−1 (Sp24) were taken into consideration. Seasons were divided into four phases (P): P1 (matches 1–10), P2 (11–19), P3 (20–29), and P4 (30–38). The results showed that young players covered significantly greater TD, HIRD and VHIRD than the rest of the players (p < .05) in all season phases. In addition, TD significantly decreased along season phases in all player age group (p < .01). Crucially, young players performed significantly greater numbers of Sp21 and Sp24 than the rest of the players (p < .05) in all season phases. In addition, Sp21 and SP24 significantly decreased in middle-aged (p < .01) and senior players (p < .05) across the seasons. This study demonstrated that players’ match running performance decreases with increasing years, especially in high-intensity running distances.

Penelitian ini bertujuan untuk mengetahui adakah Pengaruh Media Pembelajaran Pop Up Book terhadap hasil belajar siswa kelas V SDN Ciangsana 04 Bogor. Penelitian ini merupakan jenis penelitian kuantitatif dengan metode penelitian yang digunakan yaitu metode quasi eksperimen. Populasi pada penelitian ini adalah kelas V SDN Ciangsana 04 Bogor dengan sampel penelitian yaitu siswa kelas V SDN Ciangsana 04 Bogor, yang terdiri dari 2 kelas, yaitu kelas V A yang berjumlah 29 siswa, sebagai kelas eksperimen, dan dan kelas V B yang terdiri dari 25 siswa, sebagai kelas kontrol. Dengan media pembelajaran pop up book dan dikelas kontrol menggunakan media pembelajaran konvensional. Pada penelitian ini alat pengumpul data yang digunakan adalah tes pilihan ganda berjumlah 20 soal yang telah diuji validasi. Hasil penelitian ini menunjukkan bahwa hasil belajar di kelas VA yang menggunakan media pembelajaran pop up book memiliki nilai rata-rata sebesar 92,321 sedangkan pada kelas V B yang menggunakan media pembelajaran konvensional memiliki memperoleh nilai rata-rata sebesar 82,5. Dari hasil perhitungan uji perbedaan dua kelompok bebas diperoleh hasil bahwa hasil belajar kelompok siswa yang menggunakan media pop up book lebih baik dibandingkan kelompok siswa yang menggunakan media pembelajaran konvensional. Maka berdasarkan kriteria pengujian H0 ditolak dan H1 diterima. Berdasarkan hasil tersebut maka kesimpulan dari penelitian ini adalah media pembelajaran pop up book dapat meningkatkan hasil belajar siswa kelas v di sdn ciangsana 04 bogor.

Charles Fowler (1931-1995) was an important thinker whose reconstructionist philosophy of music education represents an untold view worthy of examination in the modern context. Fowler described the philosophy in his dissertation completed in 1964, based on the reconstructionist theory of Theodore Brameld. He outlined seven major objectives stating how music education can impact students, schools, and communities, and can serve as an agent of social change. This perspective was the basis for Fowler's pragmatic and progressive outlook throughout his 45-year career as teacher, researcher, writer, and arts advocate. His philosophy is presented here as another critical viewpoint of music teaching and learning, and for its impact on those who experience it. Following an introduction to Fowler and his connections to reconstructionism, his seven objectives for music education are presented, along with samples of writing showing his consistent philosophical beliefs over time, concluding with a review of his thinking while considering the future through a lens of the past. While prevailing viewpoints center on aesthetic, praxial, and pedagogical views, Fowler's reconstructionist philosophy is worthy of inclusion in the history of music education as he argued for a sociological perspective that predates most viewpoints commonly read in the field today.

The main objective of this research is to improve the tenth graders' speaking skill through storytelling technique at SMK Bhakti. This research is a two-cycle-process of classroom action research. The subject of the research was the students of tenth graders at SMK Bhakti-2. There were 20 students (12 males and 8 females). The instruments were the test, observation, interview, and diary notes. The result indicated that there was significant improvement of students' scores in the Pre-test to Post-test II. The mean of students' Pre-test scores was 48.20, and 63.30 for Post-test I. On the contrary, it was 77.70 in Post-test II. It was supported by interview, diary notes, and observation showing that there was students' interest in learning through the implementation of storytelling. It, therefore, is suggested for English teachers to make use of the technique to actively encourage and increase the students's positive learning attitude towards speaking English.

Contemporary urban development has marginalised outdoor play areas, which still function as meeting places because they occupy a physical and socio-cultural dimension of in-betweenness. The text aims at revisiting the centrality of playgrounds in housing complexes, arguing that such areas should gain visibility in the contemporary discourse on public housing. This idea is underpinned by an examination of experimental projects carried out in the 1950s-70s by Lady Allen of Hurtwood, Riccardo Dalisi, Aldo van Eyck, and Group Ludic. They tested early forms of participatory design and community empowerment assuming the role of “aesthetic operators”. What can we learn from post-war playground projects? Building on their radical methodologies, we will discuss the fleeting nature of such experiments, how neglected neighbourhoods benefitted from playgrounds as meeting places, and contemporary perspectives that link children's leisure space design with Living Lab ecosystems. Today, the artistic research of Céline Condorelli and Assemble collective shows how the playground is an essential tool for the imagination of the city of tomorrow.

Enquadramento: A formação em saúde tem sido debate em diferentes cenários especialmente pelas mudanças nos modelos de atenção à saúde, sendo a Educação Interprofissional em Saúde uma estratégia afinada para este fim. Objetivo: Analisar as visões sobre educação interprofissional e os desafios na mudança do modelo de formação profissional, conforme percebido por docentes e precetores de cursos de saúde numa universidade pública do sul do Brasil, através da participação no Programa de Educação pelo Trabalho (PET) - Saúde Interprofissionalidade. Metodologia: Pesquisa qualitativa, do tipo descritiva-exploratória, utilizando entrevistas semiestruturadas e análise temática. Resultados: As experiências no programa provocaram novas perceções sobre o trabalho em equipa, colaborativo e uni profissional destacando a Educação Interprofissional (EIP) como fundamental na formação e trabalho. Conclusão: Integrar a colaboração interprofissional na educação é crucial para mudanças curriculares significativas, como visto no Programa de Educação pelo Trabalho (PET). Isso impulsiona o trabalho colaborativo no Sistema Único de Saúde (SUS) através da Educação Interprofissional (EIP), impactando o perfil profissional na saúde.

Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene–phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.

Vortices belong to the most important phenomena in fluid dynamics and play an essential role in many engineering applications. They can act detrimentally by harnessing the flow energy and reducing the efficiency of an aerodynamic device, whereas in other cases, their presence can be exploited to achieve targeted flow conditions. The control of the vortex parameters is desirable in both cases. In this paper, we introduce an optimization strategy for the control of vortices in the wake of a bluff body. Flow modelling is based on RANS and DES computations, validated by experimental data. The algorithm for vortex identification and characterization is based on the triple decomposition of motion. It produces a quantitative measure of vortex strength which is used to define the objective function in the optimization procedure. It is shown how the shape of an aerodynamic device can be altered to achieve the desired characteristics of vortices in its wake. The studied case is closely related to flame holders for combustion applications, but the conceptual approach has a general applicability to vortex control.

In the Pistoia Nursery-Ornamental Rural District (Italy), a leader in Europe in ornamental nurseries covering over 5200 hectares with over 2500 different species of plant, plant-parasitic nematodes represent a serious concern. The potential efficacy of a pot cultivation system using commercial substrates to control plant-parasitic nematodes was assessed. On two different plant species, two different pot cultivation managements, potted plants, and potted plants previously cultivated in natural soil were compared to plants only cultivated in natural soil. The entire soil nematode structure with and without plants was evaluated. The relationship between soil properties and soil nematode community was investigated. All the studied substrates were free from plant-parasitic nematodes. Regarding free-living nematodes, Peat–Pumice showed nematode assemblage established by colonizer and extreme colonizer bacterial feeders, whereas Peat–Perlite included both bacterial and fungal feeders, and, finally, coconut fiber also included omnivores and predators. In farming, the substrates rich in organic matter such as coconut fiber could still play an important role in suppressing plant-parasitic nematodes because of the abundance of free-living nematodes. In fact, they are of crucial importance in both the mineralization of organic matter and the antagonistic control of plant-parasitic nematodes. Potting systems equally reduce virus-vector nematodes and improve the prey/predator ratio favoring natural control.

Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3–5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.