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1.
Polymers (Basel) ; 16(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38732664

ABSTRACT

The lifespan of an electrical transformer, primarily determined by the condition of its solid insulation, is well known under various operating conditions when mineral oil is the coolant in these machines. However, there is a trend toward replacing this oil with biodegradable fluids, especially esters; therefore, an understanding of the ageing of solid insulation with these fluids is essential. Currently available data do not allow for the selection of the best ester among those available on the market, as each study applies different conditions, making it impossible to compare results. Thus, this paper analyses the degradation of Kraft and Thermally Upgraded Kraft papers with the following five most promising commercial esters: sunflower, rapeseed, soybean, palm, and synthetic. The materials underwent accelerated thermal ageing at 130, 150, and 170 °C, and the integrity of the papers was evaluated through their polymerisation degree and the obtaining of the degradation kinetic models. The wide range of materials studied in this work, which were subjected to the same treatments, allows for a comparison of the esters, revealing significant differences in the impact of the alternative fluids. Sunflower, rapeseed, and soybean esters provided the best paper protection, i.e., the degree of polymerisation of Kraft paper in the tests at 150 °C decreased by 71% with these fluids, compared to the 83% reduction with mineral oil, 79% reduction with palm ester, and 75% reduction with synthetic ester. Furthermore, different kinetic models were obtained to predict the degradation; it was concluded that the Emsley model provides the best fit. Additionally, it was found that the behaviour of a dielectric fluid with one type of paper cannot be extrapolated, which is only noticeable in broad-scope studies.

2.
Infect Dis Ther ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733493

ABSTRACT

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children under one year of age. In high-income countries, RSV infections cause a significant overload of care every winter, imposing a significant burden to the healthcare system, which has made the development of prevention strategies a major global health priority. In this context, a new bivalent RSV prefusion F protein-based vaccine (RSVpreF) has recently been approved. The objective of this study was to evaluate the cost-effectiveness of vaccinating pregnant women with the RSVpreF vaccine to prevent RSV in infants from the Spanish National Healthcare System (NHS) perspective. METHODS: A hypothetical cohort framework and a Markov-type process were used to estimate clinical outcomes, costs, quality-adjusted life years (QALY) and cost-per-QALY gained (willingness-to-pay threshold: €25,000/QALY) for newborn infants born to RSV-vaccinated versus unvaccinated mothers over an RSV season. The base case analysis was performed from the NHS perspective including direct costs (€2023) and applying a discount of 3% to future costs and outcomes. To evaluate the robustness of the model, several scenarios, and deterministic and probabilistic analyses were carried out. All the parameters and assumptions were validated by a panel of experts. RESULTS: The results of the study showed that year-round maternal vaccination program with 70% coverage is a dominant option compared to no intervention, resulting in direct cost savings of €1.8 million each year, with an increase of 551 QALYs. Maternal vaccination could prevent 38% of hospital admissions, 23% of emergency room visits, 19% of primary care visits, and 34% of deaths due to RSV. All scenario analyses showed consistent results, and according to the probabilistic sensitivity analysis (PSA), the probability of maternal vaccination being cost-effective versus no intervention was 99%. CONCLUSIONS: From the Spanish NHS perspective, maternal vaccination with bivalent RSVpreF is a dominant alternative compared with a non-prevention strategy.

3.
Endocrinol Diabetes Nutr (Engl Ed) ; 71(1): 4-11, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38388076

ABSTRACT

INTRODUCTION: Patients with incomplete response to initial therapy of thyroid cancer can be managed with ongoing observation or potentially additional therapies. Our aim was to assess the effect of a second radioactive iodine treatment (RAIT) and its relationship with causes and clinical variables. MATERIAL AND METHODS: Patients undergoing a second RAIT for biochemical or structural incomplete response to initial therapy of DTC were retrospectively included (n=120). They were categorised based on the American Thyroid Association (ATA) classification of response to initial therapy. Patients were reclassified in the following 6-18 months after second RAIT based on imaging findings and measurements of thyroglobulin and antithyroglobulin antibody levels. The associations of a downgrading of response category and progression-free survival (PFS), and the related variables, were evaluated. RESULTS: Sixty-six patients (55%) had a downgrading on ATA response category after second RAIT. A significant interdependence of causes for second RAIT and outcomes was found (χ2=29.400, p=0.001), with patients with neck reoperation showing a higher rate of indeterminate or excellent responses. A significant association between ATA response to second RAIT and absence of structural progression was found (χ2=44.914, p<0.001), with less structural progression in patients with downgrading on ATA response (χ2=30.914, p<0.001). There was also significant interdependence to some clinical variables, such as AJCC stage (χ2=8.460, p=0.015), ATA risk classification (χ2=10.694, p=0.005) and initial N stage (χ2=8.485, p=0.004). CONCLUSIONS: In selected cases, a second RAIT could lead to more robust responses with a potential improvement in prognosis in patients with incomplete response to initial DTC treatment.


Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Humans , United States , Thyroid Neoplasms/surgery , Iodine Radioisotopes/therapeutic use , Retrospective Studies , Thyroidectomy
4.
Plant Reprod ; 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37966579

ABSTRACT

Plant architecture is an important feature for agronomic performance in crops. In maize, which is a monoecious plant, separation of floral organs to produce specific gametes has been studied from different perspectives including genetic, biochemical and physiological. Maize mutants affected in floral organ development have been key to identifying genes, hormones and other factors like miRNAs important for sex determination. In this review, we describe floral organ formation in maize, representative mutants and genes identified with a function in establishing sexual identity either classified as feminizing or masculinizing, and its relationship with hormones associated with sexual organ identity as jasmonic acid, brassinosteroid and gibberellin. Finally, we discuss the challenges and scopes of future research in maize sex determination.

5.
Microorganisms ; 11(11)2023 Nov 16.
Article in English | MEDLINE | ID: mdl-38004792

ABSTRACT

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

7.
Data Brief ; 50: 109471, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37584056

ABSTRACT

The structural elements within power transformers are commonly constructed from high-density pressboard, chosen for its favourable mechanical and dielectric properties. Among these elements are the spacers employed in the windings of transformers, which endure compressive loading during operation. The spacers are immersed in dielectric fluid and exposed to high temperatures and chemical reactions over the transformer's lifespan, resulting in the degradation of their dielectric and mechanical properties. The mechanical integrity of the power transformer significantly relies on these factors; hence, it is imperative to comprehend how ageing deteriorates the mechanical response of the high-density pressboard. The present article presents experimental data on the compressive mechanical properties of a commercially available high-density pressboard, commonly employed in power transformer spacers, under various ageing conditions (induced through accelerated thermal ageing and assessed by the degree of polymerisation). These data hold potential for diverse applications. They can enhance the existing comprehension of the mechanical behaviour and degradation mechanisms of cellulosic insulation in power transformers and provide reference benchmarks for comparison with factory-obtained values by manufacturers. In the realm of engineering failure analysis, these values can be utilised to evaluate the mechanical failures of paper-based materials utilised as structural components in power transformers.

8.
Vaccine ; 41(36): 5342-5349, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37479615

ABSTRACT

BACKGROUND AND OBJECTIVES: A cost-utility analysis was conducted to assess the efficiency of implementing a PCV20 vaccination strategy in the Spanish adult population older than 60 years, for the prevention of non-bacteremic pneumococcalpneumonia (NBP) and invasive pneumococcal disease (IPD). METHODS: A Markov model, with annual cycles and a time horizon of 10 years was used. The analysis population was stratified by age and risk groups. The comparator was the sequential vaccination with the 15-valent pneumococcal conjugate vaccine (PCV15) followed by one dose of the pneumococcal polysaccharide vaccine (PPV23). The base case analysis was performed from the National Healthcare System (NHS) perspective including direct costs (€2018) and applying a discount of 3% to future costs and outcomes. Alternative scenarios explored a shorter time horizon (5 years), the societal perspective and other available vaccination strategies. All the parameters and assumptions were validated by a panel of experts. To evaluate the robustness of the model, deterministic and probabilistic sensitivity analyses (PSA) were carried out. RESULTS: The results of the study showed that the vaccination strategy with PCV20 is a dominant option compared to the sequential regimen (PCV15 + PPSV23), resulting in direct cost savings of €85.7 M over 10 years, with a small increase in quality-adjusted life years (QALYs). PCV20 vaccination avoided 2,161 cases of IPD, 19,470 of NBP and 3,396 deaths and according to the PSA, the probability of PCV20 being cost-effective compared to a sequential regimen (PCV15 + PPSV23) was 100%. CONCLUSIONS/RECOMMENDATIONS: In the Spanish adult population older than 60 years, the vaccination strategy with one dose of PCV20 is more effective and less expensive (dominant) than vaccination with a sequential schedule with PCV15 and PPSV23.


Subject(s)
Bacteremia , Pneumococcal Infections , Adult , Humans , Cost-Benefit Analysis , Spain , Pneumococcal Vaccines , Pneumococcal Infections/drug therapy , Vaccination/methods , Vaccines, Conjugate
9.
Microorganisms ; 11(6)2023 May 24.
Article in English | MEDLINE | ID: mdl-37374878

ABSTRACT

Pneumococcal disease is a major cause of morbidity/mortality worldwide, and vaccination is an important measure in its prevention. Despite European children being vaccinated with pneumococcal conjugate vaccines (PCVs), pneumococcal infections are still a major cause of morbidity/mortality in adults with risk conditions and their vaccination might be an important prevention strategy. New PCVs have been approved, but information is lacking on their potential impact in European adults. In our review, we searched PubMed, MEDLINE, and Embase for studies on the additional PCV20 serotypes (concerning incidence, prevalence, disease severity, lethality, and antimicrobial resistance) in European adults, between January 2010 and April 2022, having included 118 articles and data from 33 countries. We found that these serotypes have become more prevalent in both invasive and non-invasive pneumococcal disease (IPD and NIPD), representing a significant proportion of cases (serotypes 8, 12F, 22F) and more serious disease and/or lethality (10A, 11A, 15B, 22F), showing antimicrobial resistance (11A, 15B, 33F), and/or affecting more vulnerable individuals such as the elderly, immunocompromised patients, and those with comorbidities (8, 10A, 11A, 15B, 22F). The relevance of pneumococcal adult carriers (11A, 15B, 22F, and 8) was also identified. Altogether, our data showed an increase in the additional PCV20 serotypes' prevalence, accounting for a proportion of approximately 60% of all pneumococcal isolates in IPD in European adults since 2018/2019. Data suggest that adults, as older and/or more vulnerable patients, would benefit from vaccination with higher-coverage PCVs, and that PCV20 may address an unmet medical need.

10.
Expert Rev Vaccines ; 22(1): 545-562, 2023.
Article in English | MEDLINE | ID: mdl-37316234

ABSTRACT

INTRODUCTION: Invasive meningococcal disease (IMD) is a major health concern which can be prevented through vaccination. Conjugate vaccines against serogroups A, C, W, and Y and two protein-based vaccines against serogroup B are currently available in the European Union. AREAS COVERED: We present epidemiologic data for Italy, Portugal, Greece, and Spain using publicly available reports from national reference laboratories and national or regional immunization programs (1999-2019), aiming to confirm risk groups, and describe time trends in overall incidence and serogroup distribution, as well as impact of immunization. Analysis of circulating MenB isolates in terms of the surface factor H binding protein (fHbp) using PubMLST is discussed as fHbp represents an important MenB vaccine antigen. Predictions of potential reactivity of the two available MenB vaccines (MenB-fHbp and 4CMenB) with circulating MenB isolates are also provided as assessed using the recently developed MenDeVAR tool. EXPERT OPINION: Understanding dynamics of IMD and continued genomic surveillance are essential for evaluating vaccine effectiveness, but also prompting proactive immunization programs to prevent future outbreaks. Importantly, the successful design of further effective meningococcal vaccines to fight IMD relies on considering the unpredictable epidemiology of the disease and combining lessons learnt from capsule polysaccharide vaccines and protein-based vaccines.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup B , Humans , Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , Vaccination , Antigens, Bacterial , Serogroup , Carrier Proteins
11.
Nutrients ; 15(5)2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36904217

ABSTRACT

Breaking is a sports dance modality that will debut for the first time at the Paris 2024 Olympic Games. This dance form combines street dance steps with acrobatics and athletic elements. It complies with gender equality, maintains aesthetic appeal, and is practised indoors. The objective of this study is to assess the characteristics of body composition and nutritional status of the athletes that make up the Breaking national team. This national team was recruited, and they underwent an analysis of body composition using bioimpedance measurement and a nutritional interview status with the completion of a survey on the frequency of the consumption of sports supplements and ergogenic aids. In addition, they completed a consumption questionnaire for a series of food groups with specified protein, lipid, and carbohydrate content. After that, parameters were analyzed in relation to their nutritional status during a complete medical examination at the Endocrinology and Nutrition Service of the Sports Medicine Center of CSD. A descriptive analysis of the results obtained was carried out to find the mean values of the variables analyzed. The analytical parameters described an adequate nutritional status, except for the mean capillary determination of 25-OH-vitamin D3, which was 24.2 ng/dL (SD: 10.3). Bone mineral density values were higher than those of the general population. This is the first time that a study of these characteristics has been carried out on Breakers, so it is highly relevant to increase knowledge in this area in order to conduct nutritional interventions aimed at improving the sports performance of these athletes.


Subject(s)
Athletic Performance , Nutritional Status , Humans , Paris , Dietary Supplements , Athletes , Body Composition
12.
Neuro Oncol ; 25(6): 1113-1122, 2023 06 02.
Article in English | MEDLINE | ID: mdl-36455228

ABSTRACT

BACKGROUND: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection. METHODS: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity. RESULTS: Twenty patients received preoperative trotabresib and underwent resection with no delays or cancelations of surgery; 16 patients received maintenance trotabresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Six-month progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30. CONCLUSIONS: Trotabresib penetrates the blood-brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concomitant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Humans , Temozolomide/therapeutic use , Dacarbazine/therapeutic use , Glioma/pathology , Glioblastoma/pathology , Brain Neoplasms/pathology , Antineoplastic Agents, Alkylating/therapeutic use
13.
J Basic Microbiol ; 63(1): 51-63, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36207285

ABSTRACT

Pyocyanin is a phenazine with redox activity produced by Pseudomonas aeruginosa that is harmful to other bacteria and eukaryotic organisms by generating reactive oxygen species. Gene regulation of pyocyanin synthesis has been addressed in the PAO1 and PA14 strains and involves the three-quorum sensing systems Las, Rhl, and Pqs; the regulators RsaL, MvaU, and RpoS, and the posttranscriptional Rsm system, among others. Here, we determined how RsmA regulates pyocyanin synthesis in P. aeruginosa ID4365, an overproducer strain. We found that, in the protease peptone glucose ammonium salts medium, rsmA inactivation increases pyocyanin production compared with the wild-type strains ID4365, PAO, and PA14. We showed that RsmA regulates inversely the expression of both phz operons involved in pyocyanin synthesis; particularly the phz2 operon is positively regulated at the transcriptional level indirectly through MvaU. In addition, we found that the phz1 operon contributes mainly to pyocyanin synthesis and that RsmA negatively regulates phzM and phzS expression. Finally, we showed that translation of the sigma factor RpoS is positively regulated by RsmA, and the expression of rpoS under an independent promoter decreases pyocyanin production in the IDrsmA strain. These results indicate that RsmA regulates not only the genes for pyocyanin production but also their regulators.


Subject(s)
Pseudomonas aeruginosa , Pyocyanine , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/metabolism , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial , Bacteria/metabolism
14.
Arch. pediatr. Urug ; 93(2): e206, dic. 2022. tab
Article in Spanish | LILACS, UY-BNMED, BNUY | ID: biblio-1383653

ABSTRACT

Introducción: el intento de autoeliminación (IAE) y el suicidio han aumentado en adolescentes, es un problema de alta prioridad. Objetivo: establecer la epidemiología y su relación con factores de riesgo (FR) y protección (FP) de conducta suicida en usuarios de un Espacio Adolescente en el primer nivel de atención del subsector público (diciembre 2016-setiembre 2017). Material y método: encuesta anónima a adolescentes de ambos sexos, entre 12 y 19 años. Se compararon FR y FP entre: franjas etarias (12 a 14 años y 15 a 19 años); sexo; IAE previo versus su ausencia e institucionalización o no. Se consideró p menor a 0,05 como estadísticamente significativa. Los datos se ingresaron en Excel y se analizaron con Epi Info 7.2.0.1. Resultados: 107 entrevistados, 60 mujeres, edad: 13,3 (media); IAE previo más frecuente entre 15 y 19 años y sexo femenino (p 95%). FP p 95%: actividad recreativa, autoestima elevada, y buena resolución de problemas. FR p 95%: maltrato, abuso sexual, muerte de ser querido, consumo de sustancias y enfermedad psiquiátrica. Comparando edades, FP: familia unida, proyectos y amigos (p 95%); FR: consumo de sustancias, enfermedad psiquiátrica, maltrato, abuso sexual, familiar con enfermedad psiquiátrica, muerte de ser querido, trastorno del sueño, institucionalización, ideación y planificación suicidas (p 95%). Al comparar sexos, no se encontraron FP p 95% FR. Conclusiones: se deben estimular actividades recreativas en adolescentes y ofrecer asistencia en salud mental a aquellos que presentan FR de conducta suicida.


Introduction: self-harm (SH) and suicide have increased in adolescents, and they have become a high health priority. Objective: to establish the epidemiology and its relationship with risk factors (RF) and protection (PF) of suicidal behavior in users of a Primary Care Adolescent Center of the State Health Sector (December 2016 - September 2017). Materials and methods: confidential survey of adolescents of both sexes, between 12 and 19 years of age. We carried out a descriptive analysis in order to compare RF and PF between ages (12 to 14 and 15 to 19); sex; previous SH self-harm versus its absence and institutionalization or not. p less than 0.05 was considered statistically significant. Data were entered into Excel and analyzed using Epi Info 7.2.0.1. Results: 107 interviewees, 60 females, age: 13.3 (mean); Most frequent previous SH between 15 and 19 years and female sex (p 95%). PF p 95 %: recreational activity, high self-esteem, and good problem-solving skills. RF p 95 %: child abuse, sexual abuse, death of a loved one, substance use and mental illness. Comparing ages, PF: close family, projects and friends (p 95%); RF: substance use, mental illness, child abuse, sexual abuse, family with mental illness, death of loved one, sleep disorder, institutionalization, suicidal ideation and suicidal planning (p 95%). When comparing sexes, PF were not found p 95% as RF. Conclusions: recreational activities should be encouraged in adolescents and Mental Health assistance should be provided to those who present RF of suicidal behavior.


Introdução: tentativa de suicídio e suicídio tem aumentado na adolescência, adquirindo alta prioridade. Objetivo: estabelecer a epidemiologia e sua relação com fatores de risco (FR) e proteção (FP) de comportamento suicida em usuários do chamado "Espaço Adolescente" no Primeiro Nível de Atenção no Subsetor Público do Sistema de Saúde (dezembro 2016-setembro 2017). Materiais e métodos: inquérito anônimo aos adolescentes de ambos os sexos, entre 12 e 19 anos de idade. Foram comparados FR e FP entre: grupos de idades (12 a 14 e 15 a 19); sexo; tentativa de suicídio anterior versus sua ausência e institucionalização ou não. Considerou-se p menor a 0,05 como estatisticamente significativa. Os dados foram processados no programa Excel e utilizando-se o programa Epi Info 7.2.0.1. Resultados: 107 entrevistados, 60 do sexo feminino, idade: 13,3 (média); antecedentes de tentativa de suicídio mais frequentes entre 15 e 19 anos e sexo feminino (p 95%). FP p 95%: atividade recreativa, autoestima elevada, e boas habilidades de resolução de problemas. FR p 95%: maltrato, abuso sexual, perda de pessoa querida, consumo de substâncias e doença psiquiátrica. Comparadas as idades, FP: família unida, projetos e amigos (p 95%); FR: consumo de substâncias, doença psiquiátrica, maltrato, abuso sexual, familiar com doença psiquiátrica, perda de pessoa querida, transtorno do sono, institucionalização, ideação suicida e planejamento suicida (p 95%). Comparados ambos os sexos, não se encontraram FP p 95% FR. Conclusões: atividades recreativas devem ser estimuladas nos casos de adolescentes e assistência à Saúde Mental deve ser fornecida aos portadores de FR suicida.


Subject(s)
Humans , Male , Female , Child , Adolescent , Young Adult , Suicide/statistics & numerical data , Primary Health Care , Uruguay/epidemiology , Cross-Sectional Studies , Risk Factors , Health Surveys , Public Sector , Sex Distribution , Protective Factors
15.
Neurooncol Adv ; 4(1): vdac146, 2022.
Article in English | MEDLINE | ID: mdl-36382109

ABSTRACT

Background: Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. Methods: In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. Results: The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Conclusions: Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings.

16.
Nanomaterials (Basel) ; 12(15)2022 Aug 08.
Article in English | MEDLINE | ID: mdl-35957155

ABSTRACT

Amidst the new techniques facing the improvement of cooling and insulating efficiency and the design of electric transformers, constrained by the current technologies, one of the more promising is the substitution of traditional dielectric oils for nanofluids. Research on nanofluids for their application in transformers as a coolant and dielectric medium have been performed during the last two decades and continue today. This review tries to collect and analyze the available information in this field and to offer it already dissected to researchers, focusing on the preparation methods and how nanoparticles affect the main properties of the base fluids. Here we also addressed the influence of different parameters as particle characteristics or environmental conditions in nanofluids performance, the evolution with time of the measured properties, or the neighboring relationship of nanofluids with other transformer components. In this sense, the most reviewed articles reflect enhancements of thermal conductivity or dielectric strength, as well as an improvement of time evolution of these properties, with respect to those that are found in base fluids, and, also, a better interaction between these nanofluids and dielectric cellulosics. Thus, the use of dielectric nanofluids in transformers may allow these machines to work safer or over their design parameters, reducing the risk of failure of the electrical networks and enhancing their life expectancy. Nevertheless, these advantages will not be useful unless a proper stability of nanofluids is ensured, which is achieved in a small part of revised articles. A compendium of the preparation methodology with this aim is proposed, to be checked in future works.

17.
Hum Vaccin Immunother ; 18(5): 2079923, 2022 11 30.
Article in English | MEDLINE | ID: mdl-35703733

ABSTRACT

Greece introduced a 13-valent pneumococcal conjugate vaccine (PCV13) into the infant national immunization program in 2010 (3 + 1 schedule until June 2019). Since 2015, PCV13 has been recommended for adults aged 19-64 years with comorbidities and adults ≥65 years sequentially with 23-valent pneumococcal polysaccharide vaccine (PPSV23). We examined pneumococcal serotype distribution among Greek adults aged ≥19 years hospitalized with community-acquired pneumonia (CAP) during November 2017-April 2019. This was an interim analysis of EGNATIA, a prospective study of adult hospitalized CAP in the cities of Ioannina and Kavala. Pneumococcus was identified using cultures, BinaxNow®, serotype-specific urinary antigen detection assays (UAD-1/2). Our analysis included overall 482 hospitalized CAP patients (mean age: 70.5 years; 56.4% male). 53.53% of patients belonged to the highest pneumonia severity index (PSI) classes (IV-V). Pneumococcus was detected in 65 (13.5%) patients, with more than half (57%) of cases detected only by UAD. Approximately two-thirds of pneumococcal CAP occurred in those aged ≥65 years (n = 40, 8.3% of CAP). More than half of pneumococcal CAP (n = 35, 53.8%) was caused by PCV13 serotypes. Most frequently detected PCV13 serotypes were 3, 19A, 23F, collectively accounting for 83% of PCV13 vaccine-type (VT) CAP and 6% of all-cause CAP. Overall, 82.9% of PCV13 VT CAP occurred among persons with an indication (age/risk-based) for PCV13 vaccination. Even with a mature PCV13 childhood immunization program, a persistent burden of PCV13 VT CAP exists in Greek adults. Strategies to increase PCV13 (and higher-valency PCVs, when licensed) coverage in adults should be implemented to reduce the disease burden.


An interim analysis of a prospective study in adults hospitalized with CAP in Greece.Serotype-specific urinary antigen detection assays were used to detect pneumococcus.A persistent burden of PCV13 vaccine-type CAP was observed in Greek adults.Improved PCV13 uptake and higher-valency PCVs may reduce the pneumococcal disease burden.


Subject(s)
Community-Acquired Infections , Pneumococcal Infections , Pneumonia, Pneumococcal , Pneumonia , Adult , Infant , Humans , Male , Child , Aged , Female , Serogroup , Greece/epidemiology , Prospective Studies , Pneumococcal Vaccines , Community-Acquired Infections/prevention & control , Streptococcus pneumoniae , Pneumonia/epidemiology , Pneumonia/prevention & control , Pneumococcal Infections/prevention & control , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Vaccines, Conjugate
18.
Educ Inf Technol (Dordr) ; : 1-19, 2022 May 27.
Article in English | MEDLINE | ID: mdl-35668900

ABSTRACT

Technologies provide a differential value to the training process, allowing for the generation of new environments, methodologies and resources that make it possible to attend to students in a more appropriate way. This potential is especially relevant in matters of inclusion, where technology is sometimes an indispensable element for learning. In this paper we explore the main advantages of the use of technology for the attention to diversity, taking into consideration the level of digital competence of future teachers and their perceptions regarding its use for the implementation of inclusive strategies. The results suggest that participants have an intermediate level of digital competence, with differences according to gender, age and degree. It is also remarkable that they perceive inclusion as one of the main challenges of the education system and that technology can contribute to making teaching practice more inclusive, allowing it to be adapted to specific needs and highlighting the importance of teacher training in both digital competence and inclusion as an educational principle.

19.
Int J Mol Sci ; 23(3)2022 Jan 25.
Article in English | MEDLINE | ID: mdl-35163274

ABSTRACT

Eukarya pyruvate kinases possess glutamate at position 117 (numbering of rabbit muscle enzyme), whereas bacteria have either glutamate or lysine. Those with E117 are K+-dependent, whereas those with K117 are K+-independent. In a phylogenetic tree, 80% of the sequences with E117 are occupied by T113/K114/T120 and 77% of those with K117 possess L113/Q114/(L,I,V)120. This work aims to understand these residues' contribution to the K+-independent pyruvate kinases using the K+-dependent rabbit muscle enzyme. Residues 117 and 120 are crucial in the differences between the K+-dependent and -independent mutants. K+-independent activity increased with L113 and Q114 to K117, but L120 induced structural differences that inactivated the enzyme. T120 appears to be key in folding the protein and closure of the lid of the active site to acquire its active conformation in the K+-dependent enzymes. E117K mutant was K+-independent and the enzyme acquired the active conformation by a different mechanism. In the K+-independent apoenzyme of Mycobacterium tuberculosis, K72 (K117) flips out of the active site; in the holoenzyme, K72 faces toward the active site bridging the substrates through water molecules. The results provide evidence that two different mechanisms have evolved for the catalysis of this reaction.


Subject(s)
Pyruvate Kinase/genetics , Pyruvate Kinase/metabolism , Pyruvate Kinase/ultrastructure , Amino Acid Sequence/genetics , Animals , Apoenzymes/metabolism , Binding Sites , Catalysis , Catalytic Domain , Glutamic Acid/metabolism , Lysine/metabolism , Models, Molecular , Mycobacterium tuberculosis/enzymology , Mycobacterium tuberculosis/genetics , Phylogeny , Potassium/metabolism , Protein Conformation , Rabbits
20.
Expert Rev Pharmacoecon Outcomes Res ; 22(5): 853-867, 2022 Jul.
Article in English | MEDLINE | ID: mdl-34949148

ABSTRACT

BACKGROUND: Economic burden of community-acquired pneumonia (CAP) is recognized. Few studies have documented such burden in adults stratified by age, risk status, and by care setting. Spanish data available is scarce. METHOD: A retrospective, multicenter study in seven regions of Spain (2017-2019) was conducted. Patients ≥18 years with a primary all-cause CAP episode diagnosis were identified. Episode-level variables included risk-stratum based on presence of an immunocompromising/chronic condition, age, number and length of hospitalized and outpatient episodes, and CAP-related healthcare costs/sick leaves were included. RESULTS: 7,108 episodes [mean age (SD): 59.2 (19.6), 50.42% male, 31.0% hospitalized] were analyzed. Low-risk group accounted for 47.7% of all CAP episodes, 31.5% moderate-risk and 20.8% high-risk. Pneumococcus was identified in 42.2% of cases. Mean CAP episode length was 22.9 days for hospitalized and 13.7 days for outpatient episode. Total healthcare cost for episode was higher in inpatient vs. outpatient: €3,955 vs. €511, p < 0.001, with higher sick leave cost (€3,281 vs. €2,632, p < 0.001), respectively. CONCLUSION: CAP required hospitalization cost is high regardless of age or comorbidities for the Spanish NHS. Given that almost half of the patients in this study did not have traditional risk factors for CAP, better preventative strategies should seriously be considered.


Subject(s)
Community-Acquired Infections , Pneumonia , Adult , Community-Acquired Infections/epidemiology , Female , Health Care Costs , Hospitalization , Humans , Male , Pneumonia/epidemiology , Pneumonia/therapy , Retrospective Studies , Spain/epidemiology
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