Genetic variations in immune mediators and prostate cancer risk: A field synopsis with Bayesian calculations.

OBJECTIVE: Our study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. METHODS: We performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein-protein networks were designed for the genes and products enrolled in the results. RESULTS: As results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein-protein networks reinforced the findings on IL1B and IL18 genes. CONCLUSION: In conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

Epithelium-derived 6-nitrodopamine modulates noradrenaline-induced contractions in human seminal vesicles.

AIMS: To evaluate the basal release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles (HISV) and to characterize its action and origin. MAIN METHODS: Left HISV obtained from patients undergoing prostatectomy surgery was suspended in a 3-mL organ bath containing warmed (37 °C) and gassed (95%O2:5%CO2) Krebs-Henseleit's solution (KHS) with ascorbic acid. An aliquot of 2 mL of the supernatant was used to quantify catecholamines by LC-MS/MS. For functional studies, concentration-responses curves to catecholamines were obtained, and pEC50 and Emax values were calculated. Detection of tyrosine hydroxylase and S100 protein were also carried out by both immunohistochemistry and fluorescence in-situ hybridization assays (FISH). KEY FINDINGS: Basal release of 6-ND was higher than the other catecholamines (14.76 ± 14.54, 4.99 ± 6.92, 3.72 ± 4.35 and 5.13 ± 5.76 nM for 6-ND, noradrenaline, adrenaline, and dopamine, respectively). In contrast to the other catecholamines, the basal release of 6-ND was not affected by the sodium current (Nav) channel inhibitor tetrodotoxin (1 µM; 10.4 ± 8.9 and 10.4 ± 7.9 nM, before and after tetrodotoxin, respectively). All the catecholamines produced concentration-dependent HISV contractions (pEC50 4.1 ± 0.2, 4.9 ± 0.3, 5.0 ± 0.3, and 3.9 ± 0.8 for 6-ND, noradrenaline, adrenaline, and dopamine, respectively), but 6-ND was 10-times less potent than noradrenaline and adrenaline. However, preincubation with very low concentration of 6-ND (10-8 M, 30 min) produced significant leftward shifts of the concentration-response curves to noradrenaline. Immunohistochemical and FISH assays identified tyrosine hydroxylase in tissue epithelium of HISV strips. SIGNIFICANCE: Epithelium-derived 6-ND is the major catecholamine released from human isolated seminal vesicles and that modulates smooth muscle contractility by potentiating noradrenaline-induced contractions.

Lean methodology: contributions to improving work processes in health and nursing.

OBJECTIVE: to investigate the contributions of applying the Lean methodology to improve work processes in health and nursing and its impact on associated financial aspects. METHOD: an integrative review, carried out in six databases, whose sample of ten (100.0%) studies was analyzed and summarized descriptively. RESULTS: the outcomes obtained were stratified into: benefits/barriers to Lean Healthcare implementation; economic aspects involving Lean Healthcare implementation; and process improvements through Lean Healthcare implementation. The majority of studies (60.0%) were carried out in university hospitals, contexts that need to continually improve the quality of services provided, generally with scarce and limited resources, which support the viability of maintaining the teaching, research and extension tripod. CONCLUSION: three (30.0%) studies highlighted the financial aspects associated with Lean methodology application. The others only mentioned the possibility of financial gains through improving processes and reducing waste.

Inclusão social pelo trabalho: percepções da primeira experiência de emprego em jovens de baixa renda / Social inclusion through work: perceptions of the first employment experience in low income young people / Inclusión social a través del trabajo: percepciones de la primera experiencia laboral en jóvenes de bajos ingresos

OBJETIVO: Este estudo teve como objetivo propor um modelo cognitivo/explicativo que represente as mudanças que podem ser incorporadas à vida de jovens de baixa renda, a partir de sua primeira experiência de emprego formal. MÉTODO: A amostra do estudo foi composta por 25 jovens beneficiários do Programa Primeiro Emprego/BA, que participaram de grupos focais on-line. Para a análise, as falas foram inicialmente categorizadas por meio da análise de conteúdo temática e, em seguida, visando uma sistematização e o estabelecimento de uma relação entre as categorias adotadas, foi utilizada a técnica do mapeamento cognitivo. RESULTADOS: A partir da análise das falas dos jovens, foram identificados 29 núcleos de sentidos, distribuídos em torno da tríade indivíduo- trabalho-sociedade. Entre as mudanças pessoais percebidas, destacam-se a valorização e o crescimento pessoal, assim como questões financeiras. Nas mudanças laborais, o aumento da empregabilidade como resultado da maior qualificação profissional e das novas habilidades técnicas adquiridas foi amplamente citado. Por fim, no que diz respeito às mudanças sociais, a percepção de alteração do status social ficou evidente. A maioria das mudanças observadas foram positivas e indicaram um aumento na qualidade de vida dos jovens de baixa renda. CONCLUSÃO: Conclui-se, portanto, que para uma modificação dos padrões de reprodução da força de trabalho juvenil, baseados na precarização e na subalternidade, é necessária uma transformação da realidade laboral dos seus atores.

OBJECTIVE: This study aimed to propose a cognitive/explanatory model that represents the changes that can be incorporated into the lives of low-income young people, from their first experience of formal employment. METHOD: The study sample consisted of 25 young beneficiaries of the First Employment Program/ BA, who participated in online focus groups. For the analysis, the speeches were initially categorized through thematic content analysis and, then, aiming at systematization and the establishment of a relationship between the adopted categories, the cognitive mapping technique was used. RESULTS: Based on the analysis of the young people's statements, 29 nuclei of meanings were identified, and distributed around the individual-work-society triad. Among the perceived personal changes, valorization and personal growth stand out, as well as financial issues. In terms of job changes, the increase in employability as a result of higher professional qualifications and new technical skills acquired was widely cited. Finally, with regard to social changes, the perception of change in social status was evident. Most of the changes observed were positive and indicated an increase in the quality of life of low-income youth. CONCLUSION: It is concluded, therefore, that for a change in the system, a transformation of the work reality of its actors is necessary.

OBJETIVO: Este estudio tuvo como objetivo proponer un modelo cognitivo/explicativo que represente los cambios que pueden incorporarse en la vida de jóvenes de bajos ingresos, a partir de su primera experiencia de empleo formal. MÉTODO: La muestra del estudio estuvo compuesta por 25 jóvenes beneficiarios del Programa Primeiro Emprego/BA, que participaron de grupos focales en línea. Para el análisis, los enunciados fueron inicialmente categorizados a través del análisis de contenido temático y luego, con el objetivo de sistematizar y establecer una relación entre las categorías adoptadas se utilizó la técnica del mapeo cognitivo. RESULTADOS: A partir del análisis de los enunciados de los jóvenes, se identificaron 29 centros de significado, distribuidos en torno a la tríada individuo-trabajo-sociedad. Entre los cambios personales percibidos se destacan la apreciación y el crecimiento personal, así como las cuestiones financieras. En los cambios laborales se citó ampliamente el aumento de la empleabilidad como consecuencia de una mayor cualificación profesional y de nuevas competencias técnicas adquiridas. Finalmente, en lo que respecta a los cambios sociales, se hizo evidente la percepción de cambios en el estatus social. La mayoría de los cambios observados fueron positivos e indicaron un aumento en la calidad de vida de los jóvenes de bajos ingresos. CONCLUSIÓN: Se concluye, por tanto, que para modificar los patrones de reproducción de la fuerza laboral juvenil, basados en la precariedad y la subalternidad, es necesaria una transformación de la realidad laboral de sus actores.

Assessing the Time Evolution of COVID-19 Effective Reproduction Number in Brazil.

In this paper, we use a Bayesian method to estimate the effective reproduction number ( R ( t ) ), in the context of monitoring the time evolution of the COVID-19 pandemic in Brazil at different geographic levels. The focus of this study is to investigate the similarities between the trends in the evolution of such indicators at different subnational levels with the trends observed nationally. The underlying question addressed is whether national surveillance of such variables is enough to provide a picture of the epidemic evolution in the country or if it may hide important localized trends. This is particularly relevant in the scenario where health authorities use information obtained from such indicators in the design of non-pharmaceutical intervention policies to control the epidemic. A comparison between R ( t ) estimates and the moving average (MA) of daily reported infections is also presented, which is another commonly monitored variable. The analysis carried out in this paper is based on the data of confirmed infected cases provided by a public repository. The correlations between the time series of R ( t ) and MA in different geographic levels are assessed. Comparing national with subnational trends, higher degrees of correlation are found for the time series of R ( t ) estimates, compared to the MA time series. Nevertheless, differences between national and subnational trends are observed for both indicators, suggesting that local epidemiological surveillance would be more suitable as an input to the design of non-pharmaceutical intervention policies in Brazil, particularly for the least populated states.

Effect of Water Absorption and Stacking Sequences on the Tensile Properties and Damage Mechanisms of Hybrid Polyester/Glass/Jute Composites.

The aim of this work is to analyze the effect of water absorption on the mechanical properties and damage mechanisms of polyester/glass fiber/jute fiber hybrid composites obtained using the compression molding and vacuum-assisted resin transfer molding (VARTM) techniques with different stacking sequences. For this purpose, the mechanical behavior under tensile stress of the samples was evaluated before and after hygrothermal aging at different temperatures: TA, 50 °C, and 70 °C for a period of 696 h. The damage mechanism after the mechanical tests was evaluated using SEM analysis. The results showed a tendency for the mechanical properties of the composites to decrease with exposure to an aqueous ambient, regardless of the molding technique used to conform the composites. It was also observed that the stacking sequence had no significant influence on the dry composites. However, exposure to the aqueous ambient led to a reduction in mechanical properties, both for the molding technique and the stacking sequence. Damage such as delamination, fiber pull-out, fiber/matrix detachment, voids, and matrix removal were observed in the composites in the SEM analyses.

GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens.

Introduction: The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with Nω-nitro-L-arginine methyl ester (L-NAME). Methods: In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results and Discussion: Pre-incubation (30 min) of the tissues with GKT137831 (1 µM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 µM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (H2O2) (100 µM) increased 6-ND basal release, whereas pre-incubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30 min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 µM) or uric acid (1 mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUA with L-NAME (100 µM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and H2O2. The results obtained indicate a major role of endogenous H2O2 and peroxidases as modulators of 6- ND biosynthesis/release and a lack of peroxynitrite contribution.

Characterization of industrial TNT in ammunition shells: An in-depth study of artificial aging effects using Fourier-Transform infrared spectroscopy and gas chromatography-mass spectrometry.

In this study, we comprehensively investigated the degradation of industrial trinitrotoluene (TNT), focusing on the effects of aging and direct contact with steel surfaces, mirroring real-world usage conditions. While practical knowledge exists regarding this degradation, the existing literature lacks in-depth insights into the underlying processes. To address this gap, we conducted experiments using small steel samples, representative of military ammunition casings, which were coated with TNT and subjected to 30 days of heating at 75 °C under vacuum conditions. A subset of these samples was coated with a protective red alkyd paint. After the aging process, the TNT was carefully removed from the metal surfaces and subjected to a comprehensive analysis encompassing scanning electron microscopy, Fourier-transform infrared spectroscopy, and gas chromatography-mass spectrometry. Our results reveal a remarkable preservation of the chemical integrity of industrial TNT, even in the presence of thermal stress and direct steel contact. Although superficial changes were observed in the TNT's appearance, all analytical data consistently demonstrated the maintenance of its chemical composition. Notably, the sole change in composition was attributed to the presence of degradation products associated with the alkyd paint coating, rather than intrinsic TNT degradation. These findings underscore the negligible impact of degradation processes on TNT in scenarios involving the solid-phase thermal stress of TNT in direct contact with metal, significantly enhancing our understanding of TNT safety when packaged within steel artifacts-a common context in military ammunition.

Economic assessment of abemaciclib for the adjuvant treatment of luminal HER2- breast cancer from the perspective of the Spanish health system.

INTRODUCTION: Abemaciclib is an oral inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). Data from the clinical trial monarchE (2023) showed improved survival from invasive disease. The aim of the present article was to conduct an economic assessment of adjuvant treatment with abemaciclib in women with luminal, HER2- and node-positive breast cancer. METHODS: A Markov model was constructed with four mutually exclusive health states (disease-free, local recurrence, distal recurrence and death). Analyses were based on the clinical trial monarchE which compared an intervention group (abemaciclib + hormone therapy [HT]) with HT alone. The effectiveness measure used was quality-adjusted life years (QALY), with unit costs and utilities being obtained from existing literature. The incremental cost-utility ratio (ICUR) was used to compare the two treatment strategies. RESULTS: Total costs were €98,765 and €17,935 for the abemaciclib plus HT group and the HT alone group, respectively. The health outcome was 10.076QALY for the intervention group and 9.495QALY for the control group, with the ICUR being€139,173/QALY. CONCLUSION: Despite the significant gains of abemaciclib as adjuvant treatment in terms of progression-free survival, this treatment is not cost-effective for the Spanish National Health System at published prices. It may be cost-effective with an appropriate discount on the official price.

Finishing of grazing crossbred steers supplemented with detoxified castor bean meal (Ricinus communis L.) in the rainy-dry transition period.

This study evaluated levels of replacement of soybean meal by castor bean meal in the finishing crossbred steers on Brachiaria brizantha cv. Marandu pasture during the rainy-dry transition period. Forty Holstein-Zebu crossbred steers with an average initial weight of 395.93 ± 10 kg were randomly allocated to four treatment groups that were supplemented with concentrate levels of replacing (0, 290, 613, and 903 g/kg DM of the supplement; at 0.4% body weight [BW]). The experimental period was 120 days. A completely randomized experimental design was adopted; with regression analysis using the computational software package (SAS 9.2, USA). Intake and digestibility of dry matter (DM) and nutrients and animal performance were evaluated. The replacement levels did not influence (P > 0.05) the intakes of DM (kg/day), organic matter (OM, kg/day), neutral detergent fiber (NDF, kg/day and %BW), non-fibrous carbohydrates (NFC, kg/day), or total digestible nutrients (kg/day). However, the intake of crude protein (CP) and ether extract (EE, kg/day) decreased as the replacement levels were increased (P < 0.05). The digestibility of DM, OM, NDF, and EE did not change, whereas CP digestibility decreased linearly and NFC digestibility increased linearly (P < 0.05). The replacement levels did not affect (P > 0.05) final body weight, average daily gain, feed conversion, and carcass yield. Castor bean meal can replace up to 903 g/kg DM of soybean meal in the composition of the supplement without compromising the performance of steers on Marandu pasture during the rainy-dry transition period.

Pathological fracture induced by Halicephalobus gingivalis (Nematoda: Rhabditida) in a horse limb.

Halicephalobus gingivalis is a free-living nematode that occasionally causes infections in horses. We report a rare case of limb fracture of horse caused by infection with H. gingivalis. An 8-year-old mare was referred to the Veterinary Hospital of the Federal University of Lavras with claudication grade 5 of the right hind limb, that had been started 3 months ago. The patient had aseptic arthritis in the tarsal joint and edema that extended to the quartile. The radiographic examination showed punctate osteolysis with exacerbation of bone trabeculation along the calcaneus, talus, proximal epiphysis of the third metatarsal and distal epiphysis of the tibia. Treatment for arthritis was initiated, and the animal showed a slight improvement in limb function. However, 21 days after hospitalization, due to a comminuted fracture of the tibia, it was euthanized. At necropsy, yellowish masses were found from the metatarsal to the tibia, and around the tarsal bones and joint. Similar masses were also found in the left kidney. Numerous nematodes compatible with H. gingivalis were identified. This is the first description of a pathological fracture caused by H. gingivalis infection in an equine limb.

Sphenoid Meningoencephalocele Correction Through a Transpterygoid Approach.

Sphenoid meningoencephaloceles are rare, and their treatment is challenging. In this report, we describe two clinical cases of sphenoid meningoencephalocele, in which one patient presented with a cerebrospinal fluid leak after repeated head trauma, while in the other, sphenoid meningoencephalocele was detected during the study of memory impairment as the patient was otherwise asymptomatic. The CT scans showed bony dehiscence on the lateral wall of the sphenoid sinus filled with soft tissue that was confirmed by MRI as being herniated brain tissue. A transpterygoid endoscopic endonasal approach was performed with a multilayer reconstruction of the defect with success in both cases without perioperative complications. Imaging techniques are fundamental for diagnosis and surgical planning. Treatment using an endoscopic endonasal approach is efficient with very low morbidity.

Prospective Evaluation of the Efficacy of Isolated Balloon Eustachian Tuboplasty: Short- and Medium-term Follow-up Results Based on Tubomanometry, ETDQ-7, Tympanometry, and Valsalva Maneuver.

Introduction Balloon eustachian tuboplasty (BET) allows the treatment of the main etiology of eustachian tube disfunction (ETD). Objective To evaluate the efficacy of isolated BET, through objective and subjective results, in the short and medium term, in patients with chronic obstructive ETD. Methods Adult patients diagnosed with chronic obstructive ETD who underwent BET between January 2018 and December 2020 were enrolled in the study. We performed a prospective observational study of BET efficacy, by comparing subjective data, based on the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7), and objective data, obtained by tympanometry, objective Valsalva maneuver and tubomanometry, prior to BET with these outcome tools on postprocedure follow-up. Results In total, 30 BETs were performed and analyzed. There were no complications with the procedure. Analysis of BET efficacy was performed in the short-term (average of 7.5 weeks) and in the medium-term (average of 8 months). There was a significant reduction ( p < 0.0001) in the total ETDQ-7 score from baseline to both follow-up periods. A normalization of the ETDQ-7 score was observed in 60 and 83.3% of the performed procedures, in the short- and medium-term, respectively. In tubomanometry, we verified a significant improvement ( p < 0.0001) at all pressures, with a normalization of tubomanometry values in 53.3% and 43.3% of cases in the short- and medium-term, respectively. Tympanogram normalization occurred in 71.4% of patients with abnormal preoperative assessments. Conclusion As an isolated procedure, BET results in significant improvements in symptomatology and objective metric results. This, associated with its safety profile, currently makes BET the most indicated therapeutic option in refractory obstructive ETD.

Impacts of the first wave of the COVID-19 pandemic on leisure and transportation physical activity among healthcare workers.

Introduction: The COVID-19 pandemic may lead to reduced physical activity (PA) in health care workers (HCWs). Objective: To evaluate leisure and transport-related PA in HCW of a COVID-19-dedicated hospital during the first wave of the COVID-19 pandemic. Methods: This is a cross-sectional study with a sample of 1,527 HCWs. Socioeconomic aspects, occupational characteristics, and engagement in leisure and transport-related PA were investigated through an online survey administered in August of 2020. Results: More than 80 % HCWs performed < 150 min/week of leisure-related PA, and 85 % performed ≤ 30 min/day transport-related PA. Being male was associated with more PA (OR: 1.93; 95 % CI:1.40-2.66) and transport-related PA; working in nursing, physical therapy, and cleaning/housekeeping services was associated with low PA (OR: 0.70; 95 % CI:0.51-0.95). Physicians and administrative staff were less active in transport-related PA. Conclusions: HCWs working in a COVID-19 hospital had low levels of PA in the domains of leisure and transportation.

The pivotal role of neuronal nitric oxide synthase in the release of 6-nitrodopamine from mouse isolated vas deferens.

6-Nitrodopamine (6-ND) is released from rat and human vas deferens and is considered a major mediator of both tissues contractility. The contractions induced by 6-ND are selectively blocked by both tricyclic antidepressants and α1-adrenoceptor antagonists. Endothelial nitric oxide synthase (eNOS) is the major isoform responsible for 6-ND release in mouse isolated heart, however the origin of 6-ND in the vas deferens is unknown. Here it was investigated by LC-MS/MS the basal release of 6-ND from isolated vas deferens obtained from control, eNOS-/-, nNOS-/-, and iNOS-/- mice. In addition, it was evaluated in vitro vas deferens contractility following electric field stimulation (EFS). Basal release of 6-ND was significantly reduced in nNOS-/- mice compared to control mice, but not decreased when the vas deferens were obtained from either eNOS-/- or iNOS-/- mice. Pre-incubation of the vas deferens with tetrodotoxin (1 µM) significantly reduced the basal release of 6-ND from control, eNOS-/-, and iNOS-/- mice but had no effect on the basal release of 6-ND from nNOS-/- mice. EFS-induced frequency-dependent contractions of the vas deferens, which were significantly reduced when the tissues obtained from control, eNOS-/- and iNOS-/- mice, were pre-incubated with l-NAME, but unaltered when the vas deferens was obtained from nNOS-/- mice. In addition, the EFS-induced contractions were significantly smaller when the vas deferens were obtained from nNOS-/- mice. The results clearly demonstrate that nNOS is the main NO isoform responsible for 6-ND release in mouse vas deferens and reinforces the concept of 6-ND as a major modulator of vas deferens contractility.

Prospective Evaluation of the Efficacy of Isolated Balloon Eustachian Tuboplasty: Short- and Medium-term Follow-up Results Based on Tubomanometry, ETDQ-7, Tympanometry, and Valsalva Maneuver

Abstract Introduction Balloon eustachian tuboplasty (BET) allows the treatment of the main etiology of eustachian tube disfunction (ETD). Objective To eval uate the ef ficacy of isolated BET, through objective and subjective results, in the short and medium term, in patients with chronic obstructive ETD. Methods Adult patients diagnosed with chronic obstructive ETD who underwent BET between January 2018 and December 2020 were enrolled in the study. We performeda prospective observational study of BET efficacy, by comparing subjective data, based on the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7), and objective data, obtained by tympanometry, objective Valsalva maneuver and tubomanometry, prior to BET with these outcome tools on postprocedure follow-up. Results In total, 30 BETs were performed and analyzed. There were no complications with the procedure. Analysis of BET efficacy was performed in the short-term (average of 7.5 weeks) and in the medium-term (average of 8 months). There was a significant reduction (p < 0.0001) in the total ETDQ-7 score from baseline to both follow-up periods. A normalization of the ETDQ-7 score was observed in 60 and 83.3% of the performed procedures, in the short- and medium-term, respectively. In tubomanometry, we verified a significant improvement (p < 0.0001) at all pressures, with a normalization of tubomanometry values in 53.3% and 43.3% of cases in the short-and medium-term, respectively. Tympanogram normalization occurred in 71.4% of patients with abnormal preoperative assessments. Conclusion As an isolated procedure, BET results in significant improvements in symptomatology and objective metric results. This, associated with its safety profile, currently makes BET the most indicated therapeutic option in refractory obstructive ETD.

Lean methodology: contributions to improving work processes in health and nursing / Metodología Lean: aportes a la mejora de los procesos de trabajo en salud y enfermería / Metodologia Lean: contribuições para melhoria dos processos de trabalho em saúde e enfermagem

ABSTRACT Objective: to investigate the contributions of applying the Lean methodology to improve work processes in health and nursing and its impact on associated financial aspects. Method: an integrative review, carried out in six databases, whose sample of ten (100.0%) studies was analyzed and summarized descriptively. Results: the outcomes obtained were stratified into: benefits/barriers to Lean Healthcare implementation; economic aspects involving Lean Healthcare implementation; and process improvements through Lean Healthcare implementation. The majority of studies (60.0%) were carried out in university hospitals, contexts that need to continually improve the quality of services provided, generally with scarce and limited resources, which support the viability of maintaining the teaching, research and extension tripod. Conclusion: three (30.0%) studies highlighted the financial aspects associated with Lean methodology application. The others only mentioned the possibility of financial gains through improving processes and reducing waste.

RESUMEN Objetivo: investigar las contribuciones de la aplicación de la metodología Lean a la mejora de los procesos de trabajo en salud y enfermería y su impacto en los aspectos financieros asociados. Método: revisión integradora, realizada en seis bases de datos, cuya muestra de diez (100,0%) estudios fue analizada y resumida de forma descriptiva. Resultados: los resultados obtenidos se estratificaron en: beneficios/barreras para la implementación de Lean Healthcare; aspectos económicos que implican la implementación de Lean Healthcare; y mejoras de procesos mediante la implementación de Lean Healthcare. La mayoría de los estudios (60,0%) se realizaron en hospitales universitarios, contextos que necesitan mejorar continuamente la calidad de los servicios prestados, generalmente con recursos escasos y limitados, que sustentan la viabilidad de mantener el trípode de docencia, investigación y extensión. Conclusión: tres (30,0%) estudios destacaron los aspectos financieros asociados a la aplicación de la metodología Lean. Los demás solo mencionaron la posibilidad de obtener ganancias financieras mejorando los procesos y reduciendo el desperdicio.

RESUMO Objetivo: investigar as contribuições da aplicação da metodologia Lean para melhoria dos processos de trabalho em saúde e enfermagem e sua repercussão nos aspectos financeiros associados. Método: revisão integrativa, realizada em seis bases de dados, cuja amostra de dez (100,0%) estudos foi analisada e sintetizada descritivamente. Resultados: os desfechos obtidos foram estratificados em: benefícios/barreiras para implantação do Lean Healthcare; aspectos econômicos envolvendo a implantação do Lean Healthcare; e melhorias em processos por meio da implantação do Lean Healthcare. A maioria dos estudos (60,0%) foi realizada em hospitais universitários, contextos que precisam melhorar, continuamente, a qualidade dos serviços prestados, geralmente com recursos escassos e limitados, os quais sustentam a viabilidade da manutenção do tripé ensino, pesquisa e extensão. Conclusão: três (30,0%) estudos evidenciaram os aspectos financeiros associados à aplicação da metodologia Lean. Os demais apenas mencionaram a possibilidade de ganhos financeiros por meio da melhoria de processos e redução de desperdícios.

Assessing the Novel Mixed Tutton Salts K2Mn0.03Ni0.97(SO4)2(H2O)6 and K2Mn0.18Cu0.82(SO4)2(H2O)6 for Thermochemical Heat Storage Applications: An Experimental-Theoretical Study.

In this paper, novel mixed Tutton salts with the chemical formulas K2Mn0.03Ni0.97(SO4)2(H2O)6 and K2Mn0.18Cu0.82(SO4)2(H2O)6 were synthesized and studied as compounds for thermochemical heat storage potential. The crystallographic structures of single crystals were determined by X-ray diffraction. Additionally, a comprehensive computational study, based on density functional theory (DFT) calculations and Hirshfeld surface analysis, was performed to calculate structural, electronic, and thermodynamic properties of the coordination complexes [MII(H2O)6]2+ (MII = Mn, Ni, and Cu), as well as to investigate intermolecular interactions and voids in the framework. The axial compressions relative to octahedral coordination geometry observed in the crystal structures were correlated and elucidated using DFT investigations regarding Jahn-Teller effects arising from complexes with different spin multiplicities. The spatial distributions of the frontier molecular orbital and spin densities, as well as energy gaps, provided further insights into the stability of these complexes. Thermogravimetry, differential thermal analysis, and differential scanning calorimetry techniques were also applied to identify the thermal stability and physicochemical properties of the mixed crystals. Values of dehydration enthalpy and storage energy density per volume were also estimated. The two mixed sulfate hydrates reported here have low dehydration temperatures and high energy densities. Both have promising thermal properties for residential heat storage systems, superior to the Tutton salts previously reported.

6-Nitrodopamine is an endogenous mediator of the rabbit corpus cavernosum relaxation.

BACKGROUND: 6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that has a potent relaxant action on vascular smooth muscle in vitro. OBJECTIVES: To evaluate the basal release of 6-ND and noradrenaline from rabbit-isolated corpus cavernosum (RbCC) and its relaxing action on this tissue. METHODS: Rabbit corpus cavernosa were dissected and suspended in a 5-mL organ bath containing oxygenated Krebs-Henseleit's solution. 6-ND and noradrenaline release was quantified by liquid chromatography coupled to tandem mass spectrometry. The relaxant activity of 6-ND was assessed in RbCC strips pre-contracted with endothelin-1 (10 nM). RESULTS: Rabbit corpus cavernosum presented basal release of both 6-ND (2.9 ± 0.8 ng/mL, n = 12) and noradrenaline (1.7 ± 1.3 ng/mL, n = 12). The 6-ND release was reduced by pre-treatment with Nω -nitro-l-arginine methyl ester (l-NAME) (100 µM), whereas that of noradrenaline was unaffected. Tetrodotoxin (TTX, 1 µM) abolished the noradrenaline release but had no effect on 6-ND release, indicating a non-neurogenic origin for 6-ND. 6-ND and the selective dopamine D2 -agonist L-741,626 caused concentration-dependent RbCC relaxations (pEC50 of 11 ± 0.15 and 11.15 ± 0.28, respectively). Pre-treatment with either l-NAME or the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-on (ODQ) (100 µM) caused a rightward shift of the concentration-response curve to 6-ND, without affecting the L-741,626 responses. In TTX (100 nM)-pre-treated preparations, neither l-NAME nor ODQ shifted the 6-ND concentration-response curve. Dopamine, noradrenaline, and adrenaline caused concentration-dependent RbCC contractions. Pre-incubation with 6-ND concentration-dependently inhibited the dopamine-induced contractions, without affecting those induced by either noradrenaline or adrenaline. DISCUSSION AND CONCLUSION: 6-Nitrodopamine is the most potent endogenous relaxant agent in RbCC ever described and represents a novel mechanism by which NO causes corpus cavernosum smooth muscle relaxation. The finding that 6-ND acts as a truly selective dopamine D2 -receptor antagonist indicates that the balance of dopamine and 6-ND release/synthesis may be the main mechanism that modulates corpus cavernosum smooth muscle tonus in vivo.

Economic evaluation of adjuvant therapy with osimertinib in patients with early-stage non-small cell lung cancer and mutated EGFR.

PURPOSE: The ADAURA trial demonstrated the superiority of osimertinib over a placebo with regard to disease-free survival, showing it to be indicated as an adjuvant therapy for treatment of non-small cell lung cancer with mutated epidermal growth factor receptor (EGFR). The aim of the present study was to conduct a cost-utility analysis and an analysis of the budgetary impact of adjuvant therapy with osimertinib in patients with non-small cell lung cancer with mutated EGFR who had undergone resection surgery with curative intent. METHODS: Analyses were based on the outcomes of the ADAURA clinical trial and were conducted through a Spanish National Health Service perspective. The outcome measures used were quality-adjusted life years (QALY). RESULTS: The average overall cost of adjuvant treatment with osimertinib over a period of 100 months in the overall sample of trial patients (stages IB-IIIA) was 220,961 €, compared with 197,849 € in the placebo group. Effectiveness, estimated according to QALY, was 6.26 years in the osimertinib group and 5.96 years in the placebo group, with the incremental cost-utility ratio being 77,040 €/QALY. With regard to the budgetary impact, it was estimated that, in 2021, approximately 1130 patients would be subsidiaries to receive osimertinib. This pertains to a difference of 17,375,330 € over 100 months to fund this treatment relative to no treatment. CONCLUSION: Taking into account a Spanish threshold of 24,000 €/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 10%, to obtain a cost-effective alternative.