Clinically important pharmacokinetic drug-drug interactions with antibacterial agents.

Antimicrobial agents are widely used, and drug interactions are challenging due to increased risk of adverse effects or reduced efficacy. Among the interactions, the most important are those affecting metabolism, although those involving drug transporters are becoming increasingly known. To make clinical decisions, it is key to know the intensity of the interaction, as well as its duration and time-dependent recovery after discontinuation of the causative agents. It is not only important to be aware of all patient treatments, but also of supplements and natural medications that may also interact. Although they can have serious consequences, most interactions can be adequately managed with a good understanding of them. Especially in patients with polipharmacy it is compulsory to check them with an electronic clinical decision support database. This article aims to conduct a narrative review focusing on the major clinically significant pharmacokinetic drug-drug interactions that can be seen in patients receiving treatment for bacterial infections.

Impact of Hormone Receptor Status and Tumor Subtypes of Breast Cancer in Young BRCA Carriers.

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its impact on prognosis of young patients harboring BRCA pathogenic variant (PV). PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (≤40 years) diagnosed with invasive breast cancer and harboring germline PV in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest (disease-free survival [DFS], breast cancer specific survival [BCSS] and overall survival [OS]) were first investigated according to hormone receptors expression (positive vs. negative), and then according to breast cancer subtype (luminal A-like vs. luminal B-like vs. triple-negative vs. HER2-positive breast cancer). RESULTS: From 78 centers worldwide, 4,709 BRCA carriers were included, of whom 2,143 (45.5%) had hormone receptor-positive and 2,566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% vs. 9.6%, p<0.001), while the rate of second primary breast cancer was lower (9.1% vs. 14.7%, p<0.001) compared to patients with hormone receptor-negative disease. The 8-years DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive vs. negative disease changed over time for DFS, BCSS, and OS (p<0.05 for interactions of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-years DFS: 60.8% in luminal A-like vs. 63.5% in triple-negative vs. 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive vs. negative disease warrants consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

Pediatric conjunctival melanoma: A comprehensive case report and literature review.

Purpose: This case report aims to present a rare instance of conjunctival melanoma in a 5-year-old patient and contribute to the limited body of knowledge on pediatric conjunctival melanoma. The purpose is to understand the characteristics, diagnosis, and management of this uncommon malignancy in young individuals. Observations: The case describes a 5-year-old female with a progressively growing pigmented conjunctival lesion. The lesion was observed to be located on the temporal conjunctiva of the right eye and displayed distinctive features, including feeder vessels. Imaging revealed specific dimensions of the lesion and ruled out deeper invasions. Histopathological examination revealed architectural and cytologic atypia, positive immunohistochemical staining for HMB-45, and a Ki67 proliferation index of 20 %, confirming the diagnosis of conjunctival melanoma. Conclusions: Conjunctival melanoma, an uncommon malignancy even more so in pediatric patients, typically presents with pigmented growths and feeder vessels. This case underscores the need for thorough diagnosis and early intervention, as conjunctival melanoma can lead to devastating outcomes. The rarity of such cases limits our understanding of their etiology and progression. This case contributes to the literature on pediatric conjunctival melanoma and reinforces the importance of vigilance in detecting and managing ocular pigmented lesions in children.

Unifying quantification methods for sexual selection and assortative mating using information theory.

Sexual selection plays a crucial role in modern evolutionary theory, offering valuable insight into evolutionary patterns and species diversity. Recently, a comprehensive definition of sexual selection has been proposed, defining it as any selection that arises from fitness differences associated with nonrandom success in the competition for access to gametes for fertilization. Previous research on discrete traits demonstrated that non-random mating can be effectively quantified using Jeffreys (or symmetrized Kullback-Leibler) divergence, capturing information acquired through mating influenced by mutual mating propensities instead of random occurrences. This novel theoretical framework allows for detecting and assessing the strength of sexual selection and assortative mating. In this study, we aim to achieve two primary objectives. Firstly, we demonstrate the seamless alignment of the previous theoretical development, rooted in information theory and mutual mating propensity, with the aforementioned definition of sexual selection. Secondly, we extend the theory to encompass quantitative traits. Our findings reveal that sexual selection and assortative mating can be quantified effectively for quantitative traits by measuring the information gain relative to the random mating pattern. The connection of the information indices of sexual selection with the classical measures of sexual selection is established. Additionally, if mating traits are normally distributed, the measure capturing the underlying information of assortative mating is a function of the square of the correlation coefficient, taking values within the non-negative real number set [0, +∞). It is worth noting that the same divergence measure captures information acquired through mating for both discrete and quantitative traits. This is interesting as it provides a common context and can help simplify the study of sexual selection patterns.

Dalbavancin as consolidation therapy for infective endocarditis in patients with comorbidity. A real world experience.

OBJECTIVE: Infective endocarditis (IE) is a potentially life-threatening infection, the incidence of which has in creased in recent decades, particularly among elderly patients with comorbidity. The primary objective of this study was to evaluate the effectiveness of dalbavancin in the consolidation therapy of IE in patients with comorbidity six months after the end of treatment (EOT). METHODS: An observational and retrospective study was conducted on patients with a Charlson Comorbidity Index (CCI) ≥ 3 who were diagnosed with IE and received consolidation therapy with dalbavancin. RESULTS: Forty-eight patients were included, 58.3% were male, mean age of 76.2 years (IQR: 66-88), and a mean age adjusted CCI of 6.5 (IQR: 5-7.5). Definite IE was diagnosed in 77% of cases. The most frequently isolated microorganisms were Staphylococcus aureus (45.8%) followed by Enterococcus spp. (31.3%). Complications of IE were observed in 67.7% of cases, and cardiac surgery was performed in 27% of patients. The primary reason for using dalbavancin was outpatient parenteral antibiotic therapy in 85.4% of cases. The effectiveness at EOT was 93.8%. At six months, six IE-related deaths, four unrelated deaths, and two IE relapses were observed. The effectiveness was 77%. Adverse effects related to DBV were reported in 4.2% of cases, of which 2% were considered serious. CONCLUSIONS: Dalbavancin has proven to be an effective alternative as consolidation antibiotherapy for IE in elderly patients with comorbidity. Moreover, a very favorable safety profile with few associated adverse effects has been observed in this population.

Ruminal microbiome changes across lactation in primiparous Holstein cows with varying methane intensity: Heritability assessment.

Methane is a potent greenhouse gas produced during the ruminal fermentation and is associated with a loss of feed energy. Therefore, efforts to reduce methane emissions have been ongoing in the last decades. Methane production is highly influenced by factors such as the ruminal microbiome and host genetics. Previous studies have proposed to use the ruminal microbiome to reduce long-term methane emissions, as ruminal microbiome composition is a moderately heritable trait and genetic improvement accumulates over time. Lactation stage is another important factor that might influence methane production but potential associations with the ruminal microbiome have not been evaluated previously. This study sought to examine the changes in ruminal microbiome over the lactation period of primiparous Holstein cows differing in methane intensity and estimate the heritability of the abundance of relevant microorganisms. Ruminal content samples from 349 primiparous Holstein cows with 14 - 378 d in milk were collected from May 2018 to June 2019. Methane intensity (MI) of each cow was calculated as methane concentration/milk yield. Up to 64 taxonomic features (TF) from 20 phyla had a significant differential abundance between cows with low and high MI early in lactation, 16 TF during mid lactation, and none late in lactation. Taxonomical features within the Firmicutes, Proteobacteria, Melainabacteria, Cyanobacteria, Bacteroidetes and Actinobacteria phyla were associated to low MI, whereas eukaryotic TF and those within the Euryarchaeota, Verrucomicrobia, Kiritimatiellaeota, Lentisphaerae phyla were associated to high MI. Out of the 60 TF that were found to be differentially abundant between early and late lactation in cows with low MI, 56 TF were also significant when cows with low and high MI were compared in the first third of the lactation. In general, microbes associated with low MI were more abundant early in lactation (e.g., Acidaminococcus, Aeromonas and Weimeria genera) and showed low to moderate heritabilities (0.03 to 0.33). These results suggest some potential to modulate the rumen microbiome composition through selective breeding for lower MI. Differences in the ruminal microbiome of cows with extreme MI levels likely result from variations in the ruminal physiology of these cows and were more noticeable early in lactation probably due to important interactions between the host phenotype and environmental factors associated to that period. Our results suggest that the ruminal microbiome evaluated early in lactation may be more precise for MI difference, and hence, this should be considered to optimize sampling periods to establish a reference population in genomic selection scenarios.

Bibliometric study of the advances made in clinical dermatological research in Spain from 2015 through 2021: update of the MaIND project and interactive online map. / Estudio bibliométrico sobre la evolución de la investigación clínica dermatológica española entre 2015 y 2021: actualización del proyecto MaIND y mapa interactivo en línea.

INTRODUCTION: A clinical dermatological research was conducted in Spain from 2005 through 2014 as part of the MaIND project with the provinces or centers with the highest number of published articles. However, a low level of evidence in scientific production was confirmed as the overall result. The aim of this study is to update the Spanish clinical dermatological research in bibliometric terms from 2015 through 2021 with comparisons between both periods of time. MATERIAL AND METHODS: We conducted a bibliometric study to replicate the methodology used in the article to be updated. We included articles whose corresponding authors' affiliation was a Spanish dermatological center, which met the criteria for clinical research in dermatology, including a level of evidence ≤ 4. RESULTS: A total of 1674 out of the 10199 articles met the inclusion criteria. An interactive map representing quantitative and qualitative indicators calculated for the 2005-2021 is presented here. In the study period, we found an increasing trend both in the number of published articles (p < 0.002) and in the mean number of citation-years per article (p < 0.01). A total of 22 of the articles had a level of evidence > 4, with a positive trend towards more articles having a higher level of evidence (p < 0.03). Actas Dermosifilográficas still maintains its position as the journal with the highest number of articles received (18%, a total of 302 articles). CONCLUSIONS: The results of this study show that, in Spain, the scientific production of dermatology represents an upward trend in quantity, impact, and level of evidence.

Predictors of overload in parents of children with neuromuscular diseases.

Introduction: Parents of children with neuromuscular diseases experience multiple difficulties in their daily lives that affect their physical and psychological health. The risk factors for these health issues have not been sufficiently investigated. Therefore, the aim of this study was to analyze the potential predictors of overload in these parents, including QoL, somatic symptomatology, life satisfaction, psychological adjustment and certain sociodemographic variables. Methods: A cross-sectional research study was conducted among parents who are caregivers for children with NMD in Spain. A convenience sample of 110 parents who were contacted by associations and hospitals was used. Variables were evaluated using the sociodemographic questionnaire, CarerQol-7D, PHQ-15, Barthel Index, Psychological Adaptation Scale, Zarit Overload Scale and Satisfaction with Life Scale. Results: One of the most relevant findings of the present study is the identification of 3 overload groups (mild to moderate, moderate to severe, and severe overload) based on life satisfaction and somatic symptom scores within the predictive model of the discriminate analysis. Wilk's lambda of the discriminant function was 0.568, χ2 (2, n = 55) = 8.815, p < 0.001. Discussion: This study presents a model that reveals the influence of unemployment, having a child with a severe level of dependency, the presence of somatic symptomatology and life satisfaction on caregiver overload. Likewise, the caregiver's self-esteem could be a protective factor against overload.

Intraoperative effects of an alveolar recruitment manoeuvre in patients undergoing laparoscopic colon surgery.

INTRODUCTION: Pulmonary atelectasis is common in patients undergoing laparoscopic abdominal surgery under general anaesthesia, which increases the risk of perioperative respiratory complications. Alveolar recruitment manoeuvres (ARM) are used to open up the lung parenchyma with atelectasis, although the duration of their benefit has not been clearly established. The aim of this study was to determine the effectiveness of an ARM in laparoscopic colon surgery, the duration of response over time, and its haemodynamic impact. METHODS: Twenty-five patients undergoing laparoscopic colon surgery were included. After anaesthetic induction and initiation of surgery with pneumoperitoneum, an ARM was performed, and then optimal PEEP determined. Respiratory mechanics and gas exchange variables, and haemodynamic parameters, were analysed before the manoeuvre and periodically over the following 90 min. RESULTS: Three patients were excluded for surgical reasons. The alveolar arterial oxygen gradient went from 94.3 (62.3-117.8) mmHg before to 60.7 (29.6-91.0) mmHg after the manoeuvre (P < .05). This difference was maintained during the 90 min of the study. Dynamic compliance of the respiratory system went from 31.3 ml/cmH2O (26.1-39.2) before the manoeuvre to 46.1 ml/cmH2O (37.5-53.5) after the manoeuvre (P < .05). This difference was maintained for 60 min. No significant changes were identified in any of the haemodynamic variables studied. CONCLUSION: In patients undergoing laparoscopic colon surgery, performing an intraoperative ARM improves the mechanics of the respiratory system and oxygenation, without associated haemodynamic compromise. The benefit of these manoeuvres lasts for at least one hour.

Reliability and criterion-related validity of the Cooper test in pre-adolescents and adolescents: A systematic review and meta-analysis.

The Cooper test (CT) is used to assess cardiorespiratory fitness (CRF) in pre-adolescents and adolescents, although it was originally developed to assess healthy adults. The aim of this study is to examine the available scientific evidence on the reliability and criterion validity of CT when administered to pre-adolescents and adolescents. Systematic searches were performed in three electronic databases (MEDLINE/PubMed, SPORTDiscuss and Scopus). To examine reliability and validity, four separate meta-analyses were implemented, finding high heterogeneity in studies with low methodological quality. There was a paucity of research regarding absolute reliability, while studies attempting to develop or cross-validate VO2max/VO2peak equations were almost non-existent. Information on the psychometric properties of CT in pre-adolescents under 12 years of age is scarce. The findings of this review cast doubt on the usefulness of CT both in identifying CRF and in determining the impact of strategies developed to improve CRF among pre-adolescents and adolescents.

Asociación entre Calcificaciones del Complejo Estilohioideo y Síntomas Clínicos en Pacientes Atendidos en el Centro de Salud de la Universidad San Sebastián, Sede Santiago, Chile

Hoy en día es común recibir pacientes en la clínica odontológica relatando dolor uni o bilateral en la zona lateral de la cara, más específicamente en la zona de las ramas mandibulares. Este dolor puede ser muchas veces de origen dental, muscular masticatorio, de las articulaciones temporomandibulares, o incluso tonsilar. Debido a que las anteriores son patologías más frecuentes, muchas veces el clínico no considera que la causa de estos dolores podría estar asociada al síndrome de Eagle. Esta investigación se fundamentó en la necesidad de utilizar las radiografías panorámicas como herramienta para asociar dolores que no remiten a tratamientos convencionales a calcificaciones del complejo estilohioideo, muchas veces hallazgos radiográficos que no son comúnmente tomados en consideración por el clínico. El objetivo del estudio fue eterminar la asociación entre calcificaciones del complejo estilohioideo en radiografías panorámicas y sintomatología clínica dolorosa en pacientes del centro de salud de la Universidad San Sebastián, sede Santiago, Chile. Se realizó un estudio correlacional, analítico y retrospectivo en el Centro de Salud de la Universidad San Sebastián. Se tomó una muestra aleatoria de 815 radiografías y fichas clínicas asociadas, en las cuáles se analizó la presencia, tipo y ubicación de calcificaciones del complejo estilohioideo, así como, si los pacientes relataron sintomatología dolorosa asociable al Síndrome de Eagle. Posteriormente se realizó un análisis descriptivo, exploratorio e inferencial de asociación entre variables. El porcentaje de pacientes que presentó calcificaciones del complejo estilohioideo alcanzó un 85,4%, siendo la mayoría de tipo elongado (70,98%), seguida del tipo segmentado (26,72%) y muy por debajo el tipo pseudoarticulado (2,3%). Con respecto a la prevalencia de sintomatología la gran mayoría de los pacientes no presentó (96,32%), sin verse diferencias según sexo o edad. Por último, al realizar el análisis de asociación el valor de X 2 calculado fue de 3,171, menor al valor de X2 crítico tabulado de 3,841. Al obtener un X2 calculado menor a un X2 crítico tabulado se demostró que no existe una asociación entre la presencia de calcificaciones del complejo estilohioideo y sintomatología clínica asociada. Además, las prevalencias de calcificaciones y sus tipos no variaron según la edad o género, lo que no nos permitió establecer una relación causal entre las variables.

Nowadays it is very common to receive patients in the dental clinic reporting unilateral or bilateral pain in the lateral area of the face, more specifically in the mandibular rami area. The origin of this pain can often be dental, muscular, from the temporomandibular joint or even tonsillar. Because the named pathologies are more frequent, many times the clinician does not consider that the cause of this pain could be associated with Eagle syndrome. This research was based on the need to use panoramic radiographs as a tool to associate pain that does not refer to conventional treatments with calcifications of the stylohyoid complex, many times radiographic findings that are not commonly considered by the clinician. This correlational cross analytical study was carried out at San Sebastián University Health Center. A random sample of 815 radiographs and associated clinical records was taken, in which the presence, type and location of calcifications of the stylohyoid complex were analyzed, as well as whether the patients reported painful symptoms associated with Eagle syndrome. Subsequently, a descriptive, exploratory, and inferential analysis of association between variables was conducted. The percentage of patients who presented calcifications of the stylohyoid complex reached 85.4%, being the majority the elongated type (70.98%), followed by the segmented type (26.72%) and far below the pseudoarticulated type (2.3%). Regarding the prevalence of symptoms, the vast majority of patients did not present (96.32%), without seeing differences according to gender or age. Finally, when performing the association analysis, the calculated X2 value was 3.171, lower than the critical tabulated X2 value of 3.841. Obtaining a calculated X2 lower than a critical tabulated X2 showed that there is no association between the presence of calcifications of the stylohyoid complex and associated clinical symptoms. In addition, the prevalence of calcifications and their types did not vary according to age or gender, which did not allow us to establish a causal relationship between the variables.

Sink-source connectivity for restocking of Pinna nobilis in the western Mediterranean Sea.

The critically endangered endemic bivalve Pinna nobilis from the Mediterranean Sea suffered a sudden population decline after a mass mortality event in early autumn 2016. Conservation efforts aimed at preventing extinction included safeguarding resistant individuals and implementing a breeding plan to contribute to the repopulation of the species. This study utilized a model combining Lagrangian dispersion and connectivity analyses to pinpoint optimal restocking sites in the Western Mediterranean. Our approach allowed to identify locations capable of sustaining and generating larvae for broader repopulation in key areas of the Western Mediterranean Sea prior to the mass mortality event. Six important repopulation locations from Murcia, Valencia and Balearic Islands were selected for reintroduction efforts. The results obtained in this study show how the network could be self-sufficient and able to self-replenish itself of recruits. Overall, our work can be used to direct the reintroduction of resistant animals in the Western Mediterranean Sea.

Home- vs clinic-based daylight photodynamic therapy with 5-aminolevulinic acid nanoemulsion (BF-200 ALA) for actinic keratosis: A randomized, single-blind, prospective study.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting. OBJECTIVES: To determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting. METHODS: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed. RESULTS: The overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences. CONCLUSION: Self-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment.

Determination of optimal experimental conditions for accurate 3D reconstruction of the magnetization vector via XMCD-PEEM.

This work presents a detailed analysis of the performance of X-ray magnetic circular dichroism photoemission electron microscopy (XMCD-PEEM) as a tool for vector reconstruction of magnetization. For this, 360° domain wall ring structures which form in a synthetic antiferromagnet are chosen as the model to conduct the quantitative analysis. An assessment is made of how the quality of the results is affected depending on the number of projections that are involved in the reconstruction process, as well as their angular distribution. For this a self-consistent error metric is developed which allows an estimation of the optimum azimuthal rotation angular range and number of projections. This work thus proposes XMCD-PEEM as a powerful tool for vector imaging of complex 3D magnetic structures.

Update of cartilaginous tumours according to the WHO classification 2020.

Cartilaginous tumours are a large and heterogeneous group of neoplasms characterised by the presence of a chondroid matrix, with lobular growth and arcuate, ring-like or popcorn-like calcification patterns. MRI shows hyperintensity in T2-weighted sequences and a lobulated or septal relief in postcontrast images. In the WHO 2020 classification, chondral tumours are classified as benign, intermediate or malignant. Despite technological advances, they continue to pose a challenge for both the radiologist and the pathologist, being the main difficulty the differentiation between benign and malignant tumours, which is why they require a multidisciplinary approach. This paper describes the main changes introduced in the 2020 update, describes the imaging characteristics of the main cartilaginous tumours and provides the radiological keys to differentiate between benign and malignant tumours.