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This study aimed first to promote the alkylation of polyethyleneimine (PEI), developing its alkylated (quaternary) form (QA-PEI) by inserting alkyl groups into amine groups. Subsequently, polymer blends with poly(methyl methacrylate) (PMMA) were prepared via solvent casting, and finally, the physicochemical, optical, and mechanical behavior of the resulting PMMA/QA-PEI were assessed. Elemental analyses, Fourier-transform infrared spectroscopy (FT-IR), and hydrogen nuclear magnetic resonance spectroscopy (1H-NMR) confirmed that the PEI alkylation successfully converted the amine groups into quaternary ammonium groups. When added to PMMA, QA-PEI altered its coloration, making it yellow. In addition, higher contents of QA-PEI hindered PMMA transmittance and increased its opacity due to the larger QA-PEI domains. Scanning electron microscopy (SEM) images showed that PMMA and QA-PEI formed a phase-separated system, establishing a droplet-matrix morphology. The thermal and mechanical behavior showed some compatibility between PMMA and QA-PEI as thermal resistance slightly improved and PMMA glass transition temperature (Tg) decreased. The tensile strength was also improved in the PMMA/QA-PEI blends without significant change in strain at break and tensile modulus.

En un entorno laboral cada vez más complejo, la atención a la felicidad y salud en el trabajo emerge como un área fundamental de estudio. El problema abordado se centra en la escasez de análisis rigurosos de cartografía científica sobre la relación entre felicidad en el trabajo (FT) y salud mental de empleados (SM), así como su vínculo con el bienestar individual y organizacional. El propósito central consistió en aportar en el cierre de esta brecha de conocimiento mediante un análisis bibliométrico y narrativo de la literatura disponible. Para ello, se recopilaron 256 documentos sobre la relación FT-SM de las bases de datos Web of Science y Scopus. Se utilizaron técnicas de bibliometría y análisis de cocitaciones mediante el uso de la plataforma Tree of Science. Los resultados revelaron tendencias de investigación en cuatro áreas principales: satisfacción laboral, salud mental y burnout, psicología del trabajo y liderazgo. Asimismo, se plantearon implicaciones prácticas para empresarios, directivos y académicos que busquen comprender los mecanismos que influyen en el bienestar laboral, incluyendo el bienestar individual, eficacia organizacional y formulación de políticas laborales. Este estudio contribuye significativamente al entendimiento de los determinantes del bienestar laboral y ofrece recomendaciones para futuras investigaciones y prácticas laborales.

Acoustic signals, which have been utilized for decades in the spatial localization of objects, have found applications in fields as diverse as sonar for underwater navigation, communication, and object detection. Traditional methods often rely on arrays of transducers, which necessitate the use of expensive hardware and processing algorithms. An emerging alternative is the Acoustic Leaky Wave Antenna (ALWA), which is inspired by electromagnetic leaky wave antennas. ALWA technology employs a single transducer to emit directional beams that scan angular space by frequency manipulation. Conventional arrays offer cost-effectiveness and simplicity of design, but ALWAs have the advantage of operating on the principle of energy leakage, which is achieved by various mechanisms, such as uniform apertures or slits periodic along the waveguide. This technology, applicable to underwater and airborne communications, offers compact and energy-efficient solutions, which facilitate the development of the “Underwater Internet of Things” and autonomous communication systems for underwater vehicles. This work presents a parametric study of this type of antennas with axisymmetric geometry by means of a numerical solution based on the Finite Element Method. Together with analytical studies, the physical phenomenology underlying this technology will be described, including directivity, transmission and reflection parameters, beam scanning and dispersion curve. Finally, the design is validated through experiments.

Abstract Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and cognitive aging focused on selected major inflammatory biomarkers. However, inflammatory markers are regulated and influenced by each other, and it is therefore important to consider a more comprehensive panel of markers to better capture diverse immune pathways and characterize the overall inflammatory profile of individuals. We explored 23 circulating inflammatory biomarkers using data from 1,743 participants without dementia (≥ 65 years-old) from the community-based, multiethnic Washington Heights Inwood Columbia Aging Project. Using principal component analysis (PCA), we developed six inflammatory profiles (PC-1 to PC-6) based on these 23 biomarkers and tested the association of resulting inflammatory profile with cognitive decline, over up to 12 years of follow-up. PC-1 described a pro-inflammatory profile characterized by high positive loadings for pro-inflammatory biomarkers. A higher PC-1 score was associated with lower baseline cognitive performances. No association of this profile with cognitive decline was observed in longitudinal analysis. However, PC-5 characterized by high PDGF-AA and RANTES was associated with a faster cognitive decline. Among older adults, a circulating pro-inflammatory immune profile is associated with lower baseline cognitive performance, and some specific pro-inflammatory cytokines might be associated with faster cognitive decline.

Pharmacological elevation of cyclic AMP (cAMP) of cultured cumulus-oocyte complexes (COC) before or coincident with initiation of maturation has been reported to improve outcomes for various systems for in vitro production of embryos. Here it was hypothesized that artificial elevation of cAMP in the oocyte for a 2-h period of prematuration would improve developmental competence of matured oocytes and result in increased blastocyst yield and altered expression of genes important for embryonic differentiation. Treated COC were cultured for 2 h with dibutyryl cAMP (dbcAMP), a membrane-permeable form of cAMP, and 3-isobutyl-1-methylxanthine (IBMX), which inhibits phosphodiesterases that convert cAMP to ATP. Subsequently, oocytes were matured and fertilized and the resultant embryos cultured for 7.5 d. There was no effect of treatment on the percent of oocytes or cleaved embryos becoming blastocysts or on transcript abundance of EOMES, GATA4, NANOG, SOX2, or SOX17 in the blastocyst. Results do not support the use of pharmacological enhancers of cAMP concentrations in the oocyte for improving the blastocyst yield following in vitro oocyte maturation, fertilization, and embryo culture.

Abstract We interpret infinite-distance limits in the complex structure moduli space of F-theory compactifications to six dimensions in the light of general ideas in quantum gravity. The limits we focus on arise from non-minimal singularities in the elliptic fiber over curves in a Hirzebruch surface base, which do not admit a crepant resolution. Such degenerations take place along infinite directions in the non-perturbative brane moduli space in F-theory. A blow-up procedure, detailed generally in Part I of this project [1], gives rise to an internal space consisting of a union of log Calabi-Yau threefolds glued together along their boundaries. We geometrically classify the resulting configurations for genus-zero single infinite-distance limits. Special emphasis is put on the structure of singular fibers in codimension zero and one. As our main result, we interpret the central fiber of these degenerations as endpoints of a decompactification limit with six-dimensional defects. The conclusions rely on an adiabatic limit to gain information on the asymptotically massless states from the structure of vanishing cycles. We also compare our analysis to the heterotic dual description where available. Our findings are in agreement with general expectations from quantum gravity and provide further evidence for the Emergent String Conjecture.

Biogas, an alternative energy source derived from organic materials, particularly POME, is produced through anaerobic digestion. The utilization of an UASB-HCPB fermenter has successfully yielded biogas with elevated methane content. However, the produced biogas still contained a moderate amount of CO2, necessitating further purification to make the biogas suitable for engine fuel applications. The presence of CO2 must be mitigated through an absorption method. The amount of CO₂ removed from biogas required an absorption system designed to utilize environmentally friendly solvents that can operate effectively at low pressures. The absorption design is important in designing absorber columns, particularly packed column types. It requires careful consideration of flow rates and absorbent concentrations to ensure optimal performance and suitability for industrial applications. This study aims to elaborate the design, fabrication, and performance of a packed absorption column for CO2 removal utilizing K2CO3 as a solvent with MSG as a promoter. K2CO3 promoted with MSG represents an eco-friendly solvent with potential for biogas purification applications. The novelty of this study highlights a gap in integrating biogas production and purification design, wherein biogas generated from anaerobic digestion of POME undergoes purification via an absorption system. Experimental parameters included absorbent flow rates of 1, 1.5, and 2 L/min; a biogas flow rate of 20 L/min; promoter concentrations of 1, 3, and 5 %; temperatures of 35, 45, and 55 °C; and a contact time of 5 min. Results indicated that optimal CO2 removal (47.38±1.58 %) was achieved with an absorbent flow rate of 2 L/min and MSG concentration of 5 %. Based on the calibration results, the distilled water, air, and CO2 flowmeters have regression values (R²) of 0.9947, 1.0000, and 0.9253, respectively. The highest CO2 removal was 94.44 % on CO2 flow rate of 5 L/min, air flow rate of 20 L/min and absorbent flowrate of 1.8 L/min. Maximum CO2 loading (0.0081 mol CO2/mol K2CO3) was obtained at an absorbent flow rate of 1 L/min and MSG concentration of 5 %. Temperature effects revealed optimal CO2 removal (63.32±0.42 %) at 55 °C, while peak CO2 loading (0.00987 mol CO2/mol K2CO3) occurred at 45 °C. At 55 °C, the final biogas composition achieved was 94.18 % CH4, 5.81 % CO2, and 0.01 % H2S. These results indicate an increase in the effectiveness of CO2 removal and high-purity biogas products. However, future research of synergistic study is needed on the regeneration capability of monosodium glutamate-activated K2CO3 for long-term CO2 absorption. Futhermore, development of the absorption column design is also needed by considering the operating pressure. It is expected that this initial study on integrated biogas production and purification can be further developed and applied to the palm oil industry to support the implementation of sustainable zero waste technology.

Abstract Background PRO measures of symptoms in clinical trials have historically utilized visual and numerical scales but verbal descriptors may make it easier for patients to clearly differentiate between response options. This study assessed content validity and meaningful change in five verbal response scales (VRSs) used to assess chronic rhinosinusitis with nasal polyp (CRSwNP) symptom severity. Methodology This qualitative, semi-structured interview study recruited adults from the US, Germany, and China with confirmed moderate-to-severe CRSwNP. Interviews included a concept elicitation section, where participants were asked about their experience of living with CRSwNP including symptoms and health-related quality-of-life impacts, and a cognitive debriefing section, where participants were debriefed and participant understanding and real-life relevance of the CRSwNP symptom VRS content were assessed. Interview transcripts were qualitatively analyzed using thematic analysis methods. Results Among the 24 participants interviewed, the most frequently reported CRSwNP symptoms were nasal obstruction, runny nose, mucus in the throat, loss of smell and facial pain/pressure. Participants demonstrated good understanding of the CRSwNP symptom VRS instructions, items, recall period, and response options. The five CRSwNP symptom VRS items were relevant to the majority of participants’ experience of CRSwNP. At the item level, a one-category within-person improvement was the level most frequently reported by participants to be a meaningful change. Conclusion The CRSwNP symptom VRSs assess relevant and bothersome symptoms experienced by patients with moderate-to-severe CRSwNP, supporting content validity of this measure. The findings of this study provided preliminary insights into meaningful change in the VRS. Further quantitative assessment of meaningful change is needed, and psychometric evaluation of the CRSwNP symptom VRSs will be required to evaluate their appropriateness for assessment of clinical trial endpoints in patients with CRSwNP.

Abstract The current cholesterol guidelines recommend maintaining low levels of low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease (CAD). However, recent studies have suggested that both very low and very high LDL-C levels may be associated with increased mortality in the general population. We utilized data from TriNetX, a global health research network, to investigate the association between LDL-C levels and all-cause mortality in patients with CAD. CAD patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code and stratified into six LDL-C categories:

Abstract 3D skin models have been explored as an alternative method to the use of animals in research and development. Usually, human skin equivalents comprise only epidermis or epidermis/dermis layers. Herein, we leverage 3D bioprinting technology to fabricate a full-thickness human skin equivalent with hypodermis (HSEH). The collagen hydrogel-based structure provides a mimetic environment for skin cells to adhere, proliferate and differentiate. The effective incorporation of the hypodermis layer is evidenced by scanning electron microscopy, immunofluorescence, and hematoxylin and eosin staining. The transcriptome results underscore the pivotal role of the hypodermis in orchestrating the genetic expression of a multitude of genes vital for skin functionality, including hydration, development and differentiation. Accordingly, we evidence the paramount significance of full-thickness human skin equivalents with hypodermis layer to provide an accurate in vitro platform for disease modeling and toxicology studies.

ABSTRACT The Amazon, an important biodiversity hotspot, remains poorly explored in terms of its microbial diversity and biotechnological potential. The present study characterized the metabolic potential of Gram-positive strains of the Actinomycetes and Bacilli classes isolated from soil samples of an Amazon Conservation Unit. The sequencing of the 16S rRNA gene classified the strains ACT015, ACT016, and FIR094 within the genera Streptomyces, Rhodococcus, and Brevibacillus, respectively. Genome mining identified 33, 17, and 14 biosynthetic gene clusters (BGCs) in these strains, including pathways for the biosynthesis of antibiotic and antitumor agents. Additionally, 40 BGCs (62,5% of the total BGCs) were related to unknown metabolites. The OSMAC approach and untargeted metabolomics analysis revealed a plethora of metabolites under laboratory conditions, underscoring the untapped chemical diversity and biotechnological potential of these isolates. Our findings illustrated the efficacy of the metabologenomics approach in elucidating secondary metabolism and selecting BGCs with chemical novelty.IMPORTANCEThe largest rainforest in the world is globally recognized for its biodiversity. However, until now, few studies have been conducted to prospect natural products from the Amazon microbiome. In this work, we isolated three free-living bacterial species from the microbiome of pristine soils and used two high-throughput technologies to reveal the vast unexplored repertoire of secondary metabolites produced by these microorganisms.

La presente investigación traza el recorrido, a través del tiempo y del espacio, que pudo seguir el conjunto de seis floreros realizados por Gabriel de la Corte (1648-1694) que alberga el Museo del Prado. En este artículo se plantea que la descripción de estas obras realizada en una almoneda que tuvo lugar en el siglo xviii y la que se hizo en el convento de San Felipe el Real en el año 1838 se refiere a la misma serie de lienzos. A través de la ruta descrita se persigue mostrar la importancia de conocer la pro cedencia exacta de las obras del museo, no solo de las que se muestran en sus salas sino también de las que forman parte de sus depósitos y fondos.

Background: The Internet of Things (IoT) has improved many aspects that have impacted the industry and the people’s daily lives. To begin with, the IoT allows communication to be made across a wide range of devices, from household appliances to industrial machinery. This connectivity allows for a better integration of the pervasive computing, making devices “smart” and capable of interacting with each other and with the corresponding users in a sublime way. However, the widespread adoption of IoT devices has introduced some security challenges, because these devices usually run in environments that have limited resources. As IoT technology becomes more integrated into critical infrastructure and daily life, the need for stronger security measures will increase. These devices are exposed to a variety of cyber-attacks. This literature review synthesizes the current research of artificial intelligence (AI) technologies to improve IoT security. This review addresses key research questions, including: (1) What are the primary challenges and threats that IoT devices face?; (2) How can AI be used to improve IoT security?; (3) What AI techniques are currently being used for this purpose?; and (4) How does applying AI to IoT security differ from traditional methods? Methods: We included a total of 33 peer-reviewed studies published between 2020 and 2024, specifically in journal and conference papers written in English. Studies irrelevant to the use of AI for IoT security, duplicate studies, and articles without full-text access were excluded. The literature search was conducted using scientific databases, including MDPI, ScienceDirect, IEEE Xplore, and SpringerLink. Results were synthesized through a narrative synthesis approach, with the help of the Parsifal tool to organize and visualize key themes and trends. Results: We focus on the use of machine learning, deep learning, and federated learning, which are used for anomaly detection to identify and mitigate the security threats inherent to these devices. AI-driven technologies offer promising solutions for attack detection and predictive analysis, reducing the need for human intervention more significantly. This review acknowledges limitations such as the rapidly evolving nature of IoT technologies, the early-stage development or proprietary nature of many AI techniques, the variable performance of AI models in real-world applications, and potential biases in the search and selection of articles. The risk of bias in this systematic review is moderate. While the study selection and data collection processes are robust, the reliance on narrative synthesis and the limited exploration of potential biases in the selection process introduce some risk. Transparency in funding and conflict of interest reporting reduces bias in those areas. Discussion: The effectiveness of these AI-based approaches can vary depending on the performance of the model and the computational efficiency. In this article, we provide a comprehensive overview of existing AI models applied to IoT security, including machine learning (ML), deep learning (DL), and hybrid approaches. We also examine their role in enhancing the detection accuracy. Despite all the advances, challenges still remain in terms of data privacy and the scalability of AI solutions in IoT security. Conclusion: This review provides a comprehensive overview of ML applications to enhance IoT security. We also discuss and outline future directions, emphasizing the need for collaboration between interested parties and ongoing innovation to address the evolving threat landscape in IoT security.

Background: Puerto Rico (PR) has experienced significant demographic changes, characterized primarily by an aging population and an unprecedented exodus of medical doctors. Ophthalmologists are of particular concern as they commonly serve older populations, and the island has high rates of some age-related eye diseases in the United States (US). Our research aims to investigate the factors driving ophthalmologists in PR to emigrate to the mainland US. Methods: This is a cross-sectional study among ophthalmologists in PR, using survey data collected from May to June 2023. This study recruited a convenient sample of all ophthalmologists practicing in PR via outreach in person and online communities. The survey covered various types of challenges faced by ophthalmologists, their demographics, and practice details. STATA/BE 18 statistical software was used for data analysis. Statistical tests, such as chi-square and proportion tests, were performed, stratifying results by age, gender, subspecialty, geographic health districts, experience, and practice type. Results: Among 130 of the estimated 218 ophthalmologists in PR, insurance/billing issues were identified as the primary challenge to practicing in PR and the primary reason to leave PR. The challenges that were identified included required authorizations for patient care, unjustified claim rejections, and threats of contract cancellation. We found that new ophthalmologists (≤15 years of practice) faced more specific challenges than experienced ophthalmologists (>15 years of practice), such as difficulty in obtaining insurance contracts. Conclusions: Insurance/billing issues are a pervasive concern for ophthalmologists in PR. New ophthalmologists are disproportionately affected by these challenges, potentially leading some to find employment outside of PR. There is a need for targeted policies—regulation of insurance contracting and increased reimbursement from private insurance plans—to reduce insurance contracting barriers for keeping a sustainable physician workforce in PR.

This work reports on laser-processed silicon surfaces' morphological and wetting characteristics. The silicon surfaces were initially exposed to pulsed laser radiation in the femtosecond regime. The laser emitted in its fundamental wavelength (λ = 1030 nm), and the processing was carried out in air at atmospheric pressure. The surfaces were then subjected to electrochemical modification to create micro and nano porosity. The experimental conditions allowed the creation of various hybrid systems based on laser radiation and subsequent electrochemical treatment (using HF-DMSO). This procedure altered the surface wetting behavior from hydrophilic to hydrophobic due to the distinct surface morphology without needing a specific coating.

Abstract This study analyzed the factors associated with the oral health-related quality of life (OHRQOL) of 12-year-old adolescents and their relationship with unhealthy eating and sedentary behavior. Data were collected from 615 adolescents from the five largest cities in Mato Grosso do Sul, Brazil. The theoretical framework of the social determinants of oral health guided all analyses and the measurement instrument was OIDP (impact of oral health on daily performance). Multilevel logistic and negative binomial regressions were performed to test the association of OHRQOL with unhealthy eating, sedentary behavior, sociodemographic characteristics and health behaviours. Considering the sample weights, 43% of the adolescents reported some impact on OHRQOL. In the adjusted models, higher consumption of unhealthy foods (moderate and high) was associated with a prevalence of impact on OHRQOL [OR = 3.59 (95%CI 1.99; 6.46)] and higher OHRQOL severity [RR = 2.05 (95%CI 1.43; 2.94)] compared to their counterparts. Sedentary behaviour was associated with the prevalence of impact on OHRQOL [OR = 1.52 (95%CI 1.22; 1.89)] and greater severity [RR = 1.21 (95%CI 1.07; 1.37)] compared to their counterparts. Unhealthy food consumption and sedentary behavior were associated with OHRQOL. Intersectoral health public policies for healthy eating and for reducing sedentary behavior on the internet and electronic games can help in the quality of life of adolescents.

Debido a la construcción del embalse de Ricobayo (Zamora) a finales del primer tercio del siglo XX, la mayoría los pobladores de la confluencia de los ríos Tera y Esla se vieron abocados a abandonar sus localidades anegadas por las aguas. Aquella infraestructura energética trajo el progreso fruto de la producción hidroeléctrica, pero también el desarraigo más absoluto. Para acoger a los vecinos sin acomodo únicamente se construyó, en una comarca limítrofe, una localidad de nueva planta: Pueblica de Campeán. El nuevo pueblo, determinado por las carencias materiales de la posguerra civil, fue levando desde la más estricta modestia entre finales de los años 30 y comienzos de los 40. Sin embargo, su iglesia hubo de esperar una década más, quedando financiado su proyecto arquitectónico por el Ministerio de Justicia. No obstante las limitaciones económicas y una población con identidad transterrada, la autoría del templo en el sobresaliente arquitecto Luis Cubillo de Arteaga garantizó resultados arquitectónicos muy interesantes. Planteamos el análisis de este edificio, consecuencia del desarraigo y reflejo de la sociedad que lo gestó. Un templo doblemente caracterizado por el prestigio de su proyectista, y las determinaciones de una economía maltrecha y la identidad en formación de sus destinatarios.

Com o aumento da longevidade, observa-se, nos últimos anos, uma crescente preocupação com as doenças cérebro-vasculares como o acidente vascular encefálico (AVE), doença que acomete com maior frequência os indivíduos idosos, representando um grande ônus em termos socioeconômicos, pela alta incidência e prevalência de quadros com incapacidade física. O presente trabalho objetivou descrever um caso sobre a experiência com o método “mirror visual feedback” (MVF) como recurso terapêutico ocupacional na reabilitação de um paciente idoso hemiplégico, em fase crônica, no período de janeiro a fevereiro de 2013. Pôde-se observar um progresso significativo na função motora e na execução das atividades de vida diária (AVD), com desenvolvimento do bom uso funcional da mão. O presente relato de caso sugere que a reabilitação por meio do método referido acima é um modo efetivo e coadjuvante na reabilitação terapêutica ocupacional.

European sea bass (Dicentrarchus labrax) is one of the most significant species farmed in the Mediterranean, yet a very perishable product. Its quality deteriorates rapidly as a result of three mechanisms: microbial activity, chemical oxidation, and enzymatic degradation. Microbial spoilage is the mechanism that contributes most to the quality deterioration of fresh and non-processed fish. To this end, our study aims to identify for the first time the combined effect of aquatic environment and harvest method on the composition and trajectory at storage at 0 °C of the European sea bass skin microbiome. Sampling was performed in two commercial fish farms in Western (WG) and Central Greece (CG) where fish were harvested using different methods: direct immersion in ice water or a mixture of slurry ice; application of electro-stunning prior to immersion in ice water. Samples were collected on harvest day and one week post-harvest. To profile the bacterial communities in the fish skin, 16S ribosomal RNA gene sequencing was used. The results and the following analyses indicated that the aquatic environment shaped the original composition of the skin microbiome, with 815 ASVs identified in the WG farm as opposed to 362 ASVs in the CG farm. Moreover, Pseudomonas and Pseudoalteromonas dominated the skin microbiome in the WG farm, unlike the CG farm where Shewanella and Psychrobacter were the dominant genera. All these genera contain species such as Shewanella putrefaciens, Pseudomonas aeruginosa, Pseudoalteromonas spp., and Psychrobacter sp., all of which have been implicated in the deterioration and spoilage of the final product. The different harvest methods drove variations in the microbiome already shaped by the aquatic environment, with electro-stunning favoring more diversity in the skin microbiome. The aquatic environment in combination with the harvest method appeared to determine the skin microbiome trajectory at storage at 0 °C. Although Shewanella had dominated the skin microbiome in all samples one week post-harvest, the diversity and the relative abundance of genera were strongly influenced by the aquatic environment and the harvest method. This study sheds light on the hierarchy of the factors shaping the fish skin microbiome and their importance for controlling post-harvest quality of fresh fish.

Abstract Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging metabolomics demonstrates that beta cells upon CR are more energetically competent. In fact, high-resolution microscopy show that CR reduces beta cell mitophagy to increase mitochondria mass and the potential for ATP generation. However, CR beta cells have impaired adaptive proliferation in response to high fat diet feeding. Finally, we show that long-term CR delays the onset of beta cell aging hallmarks and promotes cell longevity by reducing beta cell turnover. Therefore, CR could be a feasible approach to preserve compromised beta cell structure-function during aging and diabetes.

OBJECTIVE: To describe the translation and transcultural adaptation of Hurria's chemotherapy toxicity score, a prediction tool to estimate chemotherapy toxicity in the elderly. METHODS: The original English version of the score was translated to Portuguese using the forward and backward translation technique, as described by Guilemin. RESULTS: The translation was performed by two Brazilians (a physician and a professional translator), both fluent in English. Two professionals from a specialized linguistic service, not related to the study, then carried out the backward translation. Finally, a medical committee composed of oncologists, geriatricians, and hematologists discussed the consistency of the score, choosing a final version of the instrument in Portuguese. This version was piloted-tested in medical charts in an Oncogeriatric service, with high reliability as tested by Kappa statistic test. CONCLUSION: The final version of Hurria's chemotherapy toxicity score in Portuguese proved to be an easy, clear, and quick tool, suitable for use in clinical practice.

Abstract The CYGNO experiment aims to build a large ( $$\mathcal {O}(10)$$ O ( 10 ) m $$^3$$ 3 ) directional detector for rare event searches, such as nuclear recoils (NRs) induced by dark matter (DM), such as weakly interactive massive particles (WIMPs). The detector concept comprises a time projection chamber (TPC), filled with a He:CF $$_4$$ 4 60/40 scintillating gas mixture at room temperature and atmospheric pressure, equipped with an amplification stage made of a stack of three gas electron multipliers (GEMs) which are coupled to an optical readout. The latter consists in scientific CMOS (sCMOS) cameras and photomultipliers tubes (PMTs). The maximisation of the light yield of the amplification stage plays a major role in the determination of the energy threshold of the experiment. In this paper, we simulate the effect of the addition of a strong electric field below the last GEM plane on the GEM field structure and we experimentally test it by means of a 10 $$\times $$ × 10 cm $$^2$$ 2 readout area prototype. The experimental measurements analyse stacks of different GEMs and helium concentrations in the gas mixture combined with this extra electric field, studying their performances in terms of light yield, energy resolution and intrinsic diffusion. It is found that the use of this additional electric field permits large light yield increases without degrading intrinsic characteristics of the amplification stage with respect to the regular use of GEMs.

Abstract Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547 C > T, p.R183*; c.775 C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181 A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.

Medial gastrocnemius silent contractures (MGSCs) are prevalent, notably impacting functional status and increasing the risk of foot and ankle disorders, especially among aging populations. Although traditionally managed by podiatrists and physiotherapists, the role of rehabilitation nursing in addressing MGSCs is gaining recognition. This paper elucidates the contributions of rehabilitation nursing to the functional rehabilitation of MGSC patients and underscores its vital role within the multidisciplinary team. Initially, the paper defines the clinical and physiological characteristics of MGSCs and their implications in foot and ankle disorders. It then meticulously explores rehabilitation nursing interventions—including personalized stretching regimens, vibration therapy, balance exercises, and judicious footwear selection—emphasizing their efficacy in enhancing muscle flexibility, joint mobility, and postural stability. The emphasis is on patient-centered approaches and education to foster treatment adherence and positive rehabilitation outcomes. The significance of interdisciplinary collaboration is highlighted, focusing on how rehabilitation nursing optimizes patient care and mitigates complications. The paper advocates for recognizing and integrating rehabilitation nursing in managing MGSC-related disorders, emphasizing its importance in achieving successful functional outcomes.

Abstract During their development, amphibians undergo various physiological processes that may affect their susceptibility to environmental pollutants. Naturally occurring fluctuations caused by developmental events are often overlooked in ecotoxicological studies. Our aim is to investigate how biomarkers of oxidative stress are modulated at different stages of larval development in the Amazonian amphibian species, Physalaemus ephippifer. The premetamorphosis, prometamorphosis and metamorphic climax stages were used to analyze total antioxidant capacity (ACAP), glutathione S-transferase (GST) activity, lipid peroxidation (LPO) levels and the expression of genes nrf2, gst, gsr (glutathione reductase) and gclc (glycine-cysteine ligase, catalytic subunit). Although there was no difference in ACAP and the genes expression among the studied stages, individuals from the premetamorphosis and prometamorphosis showed higher GST activity than ones under the climax. LPO levels were highest in individuals from the metamorphic climax. The present study suggests that the oxidative status changes during ontogeny of P. ephippifer tadpoles, especially during the metamorphic climax, the most demanding developmental phase. Variations in the redox balance at different developmental stages may lead to a divergent response to pollution. Therefore, we recommend that studies using anuran larvae as biomonitors consider possible physiological differences during ontogeny in their respective analyses.

Abstract Breast cancer impacts the psychological well-being of women, leaving them at risk of developing depression, anxiety, and other stress-related disorders. The Depression Anxiety Stress Scales (DASS-21) is a widely used measure, although empirical evidence regarding its psychometric properties in the breast cancer population is limited. The purpose of this study was to conduct an exhaustive analysis of the psychometric properties of the DASS-21 in a sample of Spanish women diagnosed with breast cancer. Participants were 289 breast cancer patients who completed the DASS-21 and other questionnaires measuring life satisfaction, positive and negative affect, flourishing, perceived stress, and breast cancer-specific stressors. In terms of validity evidence based on the internal structure of the DASS-21, adequate fit indices were obtained for the model based on three first-order factors (depression, anxiety, stress) and one second-order factor (general psychological distress). Reliability coefficients (McDonald’s omega) ranged from .84 to .95. Validity evidence based on relationships with other variables was also provided by moderate and strong correlations with well-being indicators and stress measures. The results support the use of the DASS-21 for measuring general psychological distress in the breast cancer context, where it may provide useful information for the design of psychological interventions with patients.

La pregunta por la identidad biográfica ha llegado a ser una de las ideas fuerza de nuestro tiempo y ha transformado nuestra propia intimidad. Es lógico pensar que también tiene su lugar en la experiencia cristiana de hoy. Tras una descripción de su definición, elementos y dinamismos, este trabajo pone en paralelo una doble búsqueda. Por una parte, describe cuál es el lugar de esta pregunta en la experiencia cristiana buscándola en testimonios de jóvenes o materiales preparados para ellos. Por otra, realiza una indagación de esta cuestión en la propuesta del magisterio del papa Francisco sobre la santidad al Pueblo de Dios y, especialmente, a los jóvenes. Sobre estos dos caminos, el trabajo termina con un balance teológico y una prospectiva pastoral en los que se sacan a la luz los núcleos teológicos que deben ser profundizados para ofrecer un cristianismo inculturado en este momento cultural.

Abstract Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent kidney genetic disorder, producing structural abnormalities and impaired function. This research investigates its evolution on mouse models, utilizing a combination of histology imaging, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) to evaluate its progression thoroughly. ADPKD has been induced in mice via PKD2 gene knockout, followed by image acquisition at different stages. Histology data provides two-dimensional details, like the cystic area ratio, whereas CT and MRI facilitate three-dimensional temporal monitoring. Our approach allows to quantify the affected tissue at different disease stages through multiple quantitative metrics. A pivotal point is shown at approximately ten weeks after induction, marked by a swift acceleration in disease advancement, and leading to a notable increase in cyst formation. This multimodal strategy augments our comprehension of ADPKD dynamics and suggests the possibility of employing higher-resolution imaging in the future for more accurate volumetric analyses.

Abstract Background Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease. Methods This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used. Results Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p

Abstract Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes.

Abstract Background Premenopausal, high-risk, hormone receptor-positive breast cancer patients are often treated with ovarian suppression in combination with aromatase inhibitors (AI). This combination has important adverse effects, particularly in sexual function, such as vaginal dryness and loss of libido. There is no effective therapy for reduced sexual function in this setting. Our study aimed to determine the efficacy and safety, particularly regarding sexual function, of a low-dose, topical testosterone gel administration. Methods This is a pilot, single-center study, designed to evaluate the efficacy of topical testosterone gel (3 mg/day) in improving sexual function in 29 premenopausal patients on ovarian suppression in combination with an AI. The primary safety endpoint was to assess serum estradiol elevation. The primary efficacy endpoint was sexual function improvement, assessed by the Female Sexual Function Index questionnaire. Results We report the results on 29 patients. Twenty-two patients (75%) completed the 3-month treatment, and seven discontinued treatment before completion, mostly due to logistical difficulties related to the COVID-19 pandemic. All patients maintained the value of baseline mass spectrometry assay for estradiol of less than 2.7 pg/mL during the undertaken measurements. We observed a significant improvement in Female Sexual Function Index measures over the visits, with an increase from a mean of 11.7 at baseline to 19.1 in the third month (p

Rationale: Colorectal cancer (CRC) is one of the most prevalent oncological diseases with high mortality. Invasive optical (endoscopic) colono- scopy has been recognized as a golden standard for the CRC diagnostics. A promising area is the development of non-invasive tools for CRC diagnosis with circular RNA (circRNA). One of the most sensitive non-invasive tools for detection of cancer RNA markers is considered to be the biosensor methods with the use of nanowire chips with oDNA probes (fragments of DNA oligonucleotides) immobilized on their surface. It has been previously shown that circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1 are associated with CRC. Aim: To determine the lower limit of concentration sensitivity of detection of CRC-associated circRNA with nanowire chips with immobilized oDNA probes, to demonstrate the usability of these chips for non-invasive detection of circRNA in plasma in the CRC diagnostics, and to establish the potential for the use of nanowire chips for the early CRC diagnosis. Methods: To ensure biospecific binding of the circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1 (the CRC markers), oDNA probes with the nucleotide sequences complementary to the target circRNA have been immobilized on the nanowire surface. At the study step 1, we detected the lower concentration limit for detection of the target molecules with the use of their analogues, i.e. synthetic model oDNA with the nucleotide sequences complementary to oDNA probes. At the study step 2, we used the nanowire chips with immobilized oDNA probes to detect the circRNA in plasma of the patients with confirmed CRC. Plasma samples from non-cancer patients were used as controls. Results: The lower concentration limit for the detection of DNA analogues of the circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1 with nanowire chips with oDNA probes was 10-16 М. The analysis of total RNA isolated from plasma of the CRC patients showed a significant increase in the signal from the sensory elements of the nanowire chip. The analysis of plasma samples from the non-cancer patients, the nanowire signal changes were non-significant indicating the absence of detectable concentrations of the circRNA in plasma of the non-cancer patients. Conclusion: We have identified the minimal detectable concentration of the circRNA hsa_circ_0136666_CBC1, hsa_circ_0031263_CBC1, and hsa_circ_0072715_CBC1, associated to the development of CRC, with nanowire chips with immobilized oDNA probes: it was 10-16 М. The experiment showed the usability of such nanowire chips for non-invasive detection of the given circRNA markers in total RNA samples isolated from plasma of CRC patients.

Varronia curassavica Jacq. is an aromatic species appertaining to the Boraginaceae family and has been mentioned for its numerous traditional uses and pharmacological properties, especially its antimicrobial and anti-inflammatory effects. The aim of the present study was to investigate the phytochemical profile and antifungal activities of the essential oils of V. curassavica, in addition to analyzing the ADMET properties of the majority components. The GC-MS analysis of V. curassavica essential oil (EOVC) comprised 97.36% of total composition, with α-pinene, β-caryophyllene, and bicyclogermacrene (44.46%, 22.87%, and 13.05%, respectively) as the main constituents among other minor/trace constituents. The antifungal activity of EOVC was evaluated against three Candida species and was observed with IC50 > 200 μg/mL. Remarkably, the combination of EOVC with fluconazole significantly reduced the IC50 required for the drug to inhibit C. tropicalis (0.003 μg/mL), C. albicans (0.7996 μg/mL), and C. krusei (17.73 μg/mL). In addition, ADME/Tox studies using α-pinene revealed that the compound poses no toxicity threats but requires caution due to its high permeability to the blood–brain barrier (BBB). Overall, the obtained results suggest that Varronia curassavica essential oil is a potentially good antifungal agent for combating fungal resistance.

Abstract Although the terms “rare diseases” (RD) and “orphan diseases” (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades.

This review summarizes findings from simulation studies on quantitative traits in plant breeding and translates these insights into practical schemes. As agricultural productivity faces growing challenges, plant breeding is central to addressing these issues. Simulations use mathematical models to replicate biological conditions, bridging theory and practice by validating hypotheses early and optimizing genetic gain and resource use. While strategies can improve trait value, they reduce genetic diversity, making a combination of approaches essential. Studies emphasize the importance of aligning strategy with trait heritability and selection timing and maintaining genetic diversity while considering genotype-environment interactions to avoid biases in early selection. Using markers accelerates breeding cycles when marker placement is precise, foreground and background selection are balanced, and QTL are effectively managed. Genomic selection increases genetic gains by shortening breeding cycles and improving parent selection, especially for low heritability traits and complex genetic architectures. Regular updates of training sets are critical, regardless of genetic architecture. Bayesian methods perform well with fewer genes and in early breeding cycles, while BLUP is more robust for traits with many QTL, and RR-BLUP proves flexible across different conditions. Larger populations lead to greater gains when clear objectives and adequate germplasm are available. Accuracy declines over generations, influenced by genetic architecture and population size. For low heritability traits, multi-trait analysis improves accuracy, especially when correlated with high heritability traits. Updates including top-performing candidates, but conserving variability enhances gains and accuracy. Low-density genotyping and imputation offer cost-effective alternatives to high-density genotyping, achieving comparable results. Targeting populations optimizes genetic relationships, further improving accuracy and breeding outcomes. Evaluating genomic selection reveals a balance between short-term gains and long-term potential and rapid-cycling genomic programs excel. Diverse approaches preserve rare alleles, achieve significant gains, and maintain diversity, highlighting the trade-offs in optimizing breeding success.

Persistent Mu?llerian duct syndrome is a very rare form of pseudohermaphroditism characterized by the presence of structures deriving from persistent Mu?llerian duct in a patient phenotypically and occasionally genotypically expressed as a normal male. Utero Inguinal Hernias are a rare entity, which in the female population reaches 1% of incidence. However, in the male population, it is directly associated with abnormalities of sexual differentiation. We present the exceptional case of a male patient with no previous diagnosis of intersexuality who is scheduled for a right inguinal repair of a hernia. During the operative management, structures compatible with the uterus, fallopian tubes, and ovaries were identified in the hernial sac. Reduction of the hernial content to the peritoneal cavity was performed and the inguinal defect was resolved with placement of a prosthetic mesh by Lichtenstein technique.

Abstract Bats provide important ecosystem services as natural predators of, for example, lepidopteran pests. Thus, it is crucial to identify ways to enhance bat populations in agricultural landscapes. It has been shown that high landscape heterogeneity can benefit bat communities in arable fields. However, to date, the relationship between bats and the surrounding landscape within a viticultural matrix has received little attention, despite moths being major pests in viticulture. Here, we investigated how bats respond to different landscape elements in three European regions: Rhineland‐Palatinate (Germany), Burgenland (Austria), and Andalusia (Spain). We recorded bat activity using passive acoustic monitoring for four nights in 94 vineyards in total. Additionally, in Germany, we recorded bat activity along transects from hedgerows up to 120 m into the vineyards to describe the change in activity with hedgerow distance. We found that bat activity decreased with distance from the hedgerow, and the strength of the response was guild‐specific. Bat species adapted to foraging in the open space decreased their activity by half at a distance of 120 m from the hedgerow into the center of the vineyard, while bats adapted to foraging along vegetation (edge‐space bats) and those adapted to feeding within and close to vegetation (narrow‐space bats) decreased their mean flight activity by more than 80% at the same distance. Moreover, the presence of hedgerows between vineyards was positively related to a higher bat activity and feeding rate in all three countries, although this effect varied by functional guild and country. For edge‐space foraging bats, hedgerows had a positive impact in all three countries, while open‐space bats only showed a significant response in Spain. Hedgerows had consistent positive effects on bat activity in vineyards across the three study regions. Our study suggests that hedgerows should be conserved and restored as key elements to support a higher bat activity. This would also benefit other important groups of animals such as bees and birds along with the ecosystem services they provide.

Background and objectives This is a protocol for a living systematic review and meta-analysis. This review will assess the effects of state-of-the-art exercise interventions designed to promote functional mobility. Therefore, after identifying all potential interventions, we will use the F.I.T.T. principles (frequency, intensity, time, type) as well as the physical and health status of the participants as moderators to analyse the mechanisms for the positive benefits of exercise interventions. The main research questions are: Which exercise types are most beneficial for improving functional mobility in various populations of older adults? Which physical exercise characteristics in terms of frequency, intensity, time and duration will achieve the greatest benefit in terms of the defined outcomes, i.e, the functional mobility of older adults? Methods The systematic literature research according to PRISMA guidelines will search databases like MEDLINE, APA Psych-Info and Web of Science. Inclusion criteria are: healthy older people ≥ 50 years, randomized-controlled trials including exercise intervention and a walking or mobility assessments (eg., TUG, SPPB) as an outcome measure. A preliminary search revealed more than 33,000 hits that will be screened by pairs of independent reviewers. The results will be summarized according to the effects regarding functional mobility and potential dose-response relations via respective meta-analysis. Conclusion The systematic review will comprise the knowledge of the existing literature with regards to the effects of the physical activity interventions compared to an active or inactive control group. We will summarize the effects with respect to the F.I.T.T.. They provide a foundation for structuring an optimal exercise training program. If possible, we will also compare interventions from the different categories (eg. cardiovascular, resistance, motor-coordinative, multicomponent or mind-body exercise) as a network analysis and report the influence of moderator variables. Based on the results evidence-based guidelines following GRADE for physical exercise interventions to improve functional mobility in older adults will be provided.

ABSTRACT Background: Spinal stenosis refers to the narrowing of the spinal canal which can generate clinical symptoms secondary to the spinal cord injury itself, or even root involvement. The traditional open surgical procedure to correct spinal stenosis is highly traumatic and risky, and with the development of surgical techniques, endoscopic procedures have been widely used in treating said stenosis, achieving good results with minimally invasive management. Aim: To conduct a literature review regarding endoscopic techniques for correcting spinal stenosis. Method: This is an integrative literature review that surveyed the PUBMED database using the following search strategy: spinal[title] AND stenosis[title] AND surgery[title]. Only randomized clinical trials published in the last 10 years were included in the sample. Results: A total of 13 articles were identified that met the previously established search strategy, all of which were included in the review. Conclusion: The reviewed studies showed that endoscopic surgery to correct spinal stenosis could offer adequate decompression of neural elements, resulting in shorter hospital stays, faster recovery and favorable operative results. Level of Evidence IV, evidence from descriptive (non-experimental) or qualitative studies.

Abstract Objective: HPV infection is considered the most common sexually transmitted virus today. The persistence of HPV is the main cause for the development of precursor lesions and cervical cancer. There are environmental and non-environmental factors that contribute to the persistence of the virus. Studies indicate a possible relationship between the vaginal microbiota (environmental factor) and the risk of high-grade cervical squamous intraepithelial lesions and cervical cancer. This study evaluates the association between the type of vaginal microbiota and the occurrence of high-grade squamous intraepithelial lesions of the cervix. Methods: Observational, longitudinal, prospective, and analytical studies carried out between 2019 and 2021, which evaluated the vaginal microbiota of patients diagnosed with high-grade cervical squamous intraepithelial lesion before and after treatment in two collections with an interval of 6 months, using scrapings and vaginal swabs. Results: In Group I (with lesions) 28 women participated and 29 in Group II (without lesions). According to Nugent, in the initial collection of Group I, 16 women (57%) had lactobacillary microbiota, eight (28%) intermediate, and four (14%) coccus. In Group II, twenty-one (75%) were lactobacillary, one (3%) was intermediate, and seven (24%) werecoccus. With p=0.03. Conclusion: According to Nugent's criteria, there was an association between the type of vaginal microbiota and the occurrence of high-grade cervical squamous intraepithelial lesions of the cervix. The same was not observed in the Donders classification. Studies with a larger sample are needed to confirm our results.

IntroductionBefore implementing a new health care strategy, it is important to assess effectiveness but also to perform an economic evaluation. The goal of the present study was to perform a comparative economic evaluation of a new strategy aimed at using proposed implementation of the Plateletworks guidance (measurement of platelet function) with usual practice (delayed time to surgery) in patients on chronic antiplatelet treatment and scheduled for surgery with neuraxial anaesthesia due to proximal femur fracture.MethodsThis is an economic evaluation carried out alongside a randomised controlled clinical trial at four centres in Spain. Patients were randomised to undergo either early platelet function-guided surgery (experimental group) or delayed surgery (control group). As AFFEcT trial results demonstrated significative difference between groups in the primary efficacy endpoint, the median time to surgery, a cost-effectiveness analysis was performed. Direct costs associated with hospitalisation until one-month post-discharge were considered and measured from a hospital perspective. All costs were reported in euros. Analyses were performed on a per protocol basis. Effectiveness outcome measures were the incremental cost and incremental cost per reduction in days to surgery. A deterministic sensitivity analysis was implemented to quantify uncertainty.ResultsA total of 156 patients were randomized to the two groups (n = 78 per group). A total of 143 patients were included in the per protocol population (75 and 68 patients in the experimental and control groups, respectively). The median time to surgery was 2.30 days (IQR: 1.53–3.73) in the experimental group and 4.87 days (4.36–5.60) in the control group (a reduction of 2.40 days). Total costs during the 1-month study perioperative period were higher in the delayed surgery group (€18,495.19) than for the early surgery group (€16,497.59). The incremental cost was negative (€1,997.60), a statistically significant difference (P

Background: REMIT is the first real-world study of mepolizumab effectiveness in patients with severe asthma (SA) in Taiwan. Objectives: The primary objective evaluated changes in clinically significant exacerbations (CSEs; defined as use of oral corticosteroids (OCS) or emergency department (ED) visits and/or hospitalizations) in the 12 months pre- and post-mepolizumab treatment. Secondary objectives assessed changes in the number of CSEs requiring ED visits/hospitalizations and daily maintenance OCS (mOCS) dosage 12 months pre- and post-mepolizumab treatment. Three- and four-component clinical remissions were analyzed based on OCS-free, exacerbation-free, and asthma control (± stability in lung function). Design: REMIT was a retrospective, observational, self-controlled study analyzing patients in Taiwan with SA who were newly prescribed subcutaneous mepolizumab 100 mg Q4W. Methods: Data were extracted from records of 15 medical centers in Taiwan for patients indexed between November 1, 2018 and October 31, 2020. Results: A total of 170 patients were included: mean age at index date, 58.7 years; 53.5% female; 100% Chinese; 7.1% with chronic rhinosinusitis with nasal polyps, 1.8% with eosinophilic granulomatosis with polyangiitis, 1.2% with hypereosinophilic syndrome; and 55.7% with blood eosinophil count >300/µL. Pre-treatment, 71.2% had ⩾2 exacerbations, and 28.7% were on mOCS; 75.3% had no prior biologic treatment, and 24.7% had switched from other biologics. Most patients (80.0%) completed ⩾10 mepolizumab doses. Following the first mepolizumab administration (index date), CSEs reduced by 46.0% (rate ratio (RR): 0.545, 95% confidence interval (CI): 0.418–0.710; p

Introduction: A healthy lifestyle during pregnancy is crucial for improving maternal and infant outcomes. Maternal-fetal attachment and maternal prenatal depression have been identified as factors influencing maternal lifestyle during pregnancy. This study aimed to investigate the relationship between maternal-fetal attachment, maternal prenatal depression, and a healthy lifestyle among pregnant women. Methods: A cross-sectional study was conducted among 224 pregnant women in their third trimester, attending an antenatal appointment at a community health center in Surakarta, Indonesia, from July to September 2019. Results: Bivariate analysis revealed significant associations between education (p = 0.024), religion (p = 0.026), employment (p = 0.012), income (p = 0.016), parity (p = 0.026), maternal depression (p

Treatment with pegylated nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (folinic acid; 5-FU/LV) has demonstrated remarkable efficacy for metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical trials. However, real-world data on the effectiveness of nal-IRI+5-FU/LV is heterogeneous and is lacking in Spain. To assess the effectiveness and safety of nal-IRI+5-FU/LV in real-life PDAC patients in Spain. A multicenter retrospective study was conducted. Patients aged ⩾18 years who had received at least one cycle of nal-IRI+5-FU/LV as second- or third-line therapy for PDAC were included. The primary endpoint was overall survival (OS) from nal-IRI+5-FU/LV treatment initiation and OS from the diagnosis of metastatic disease (metOS). Overall, 200 evaluable patients were included (⩾3 metastatic sites: 22%; liver/lung metastases: 71.5%/36.9%; and Eastern Cooperative Oncology Group 0–1: 87% at nal-IRI+5FU/LV treatment initiation). Patients received a median of four cycles of nal-IRI+5FU/LV for 2.8 months (range 1.4–7.2), and the treatment was received in the second line by 80% of the patients. The median OS was 7.2 months (6- and 12-month OS rates: 58.1% and 28.9%, respectively), with 27.2% of the patients achieving OS ⩾12 months. The median metOS was 17.5 months, with 30.2% of the patients experiencing metOS ⩾ 24 months. The median progression-free survival (PFS) was 3.7 months (6- and 12-month PFS rate: 37.6% and 15.3%, respectively). The disease control rate was 35.5%. The median CA 19-9 levels decreased by at least 50% in 28.2% of the cases during treatment. Overall, 36% of the patients experienced at least one grade 3–4 adverse event during treatment, the most common being diarrhea (42.6%) and asthenia (30.9%). This real-world study shows that treatment with nal-IRI+5-FU/LV for advanced or metastatic PDAC affords benefit in terms of survival, radiological and CA 19-9 response, and PFS comparable to that reported in the clinical trial setting with a manageable safety profile.