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Abstract Improved phenotyping in pneumonia is necessary to strengthen risk assessment. Via a feasible and multidimensional approach with basic parameters, we aimed to evaluate the effect of host response at admission on severity stratification in COVID-19 and community-acquired pneumonia (CAP). Three COVID-19 and one CAP multicenter cohorts including hospitalized patients were recruited. Three easily available variables reflecting different pathophysiologic mechanisms—immune, inflammation, and respiratory—were selected (absolute lymphocyte count [ALC], C-reactive protein [CRP] and, SpO2/FiO2). In-hospital mortality and intensive care unit (ICU) admission were analyzed as outcomes. A multivariable, penalized maximum likelihood logistic regression was performed with ALC ( 60 mg/L), and, SpO2/FiO2 (

Normal aging presents subtle cognitive changes that can be detected before meeting the criteria for Mild cognitive impairment (MCI). Older people with low cognitive reserve and who receive limited cognitive stimulation are at greater risk of deterioration. In this regard, cognitive stimulation (CS) has been identified as an intervention that reduces this risk, provided that its design takes into account the differences in the level of cognitive reserve (CR) acquired throughout life and the baseline level of cognitive functioning. The general objective of this study is to evaluate, through a randomized clinical trial, the effectiveness of a computerized cognitive stimulation program, designed and adapted from Occupational Therapy based on the level of cognitive reserve in older adults in Primary Care. 100 participants will be randomized in a stratified manner according to the level of cognitive reserve (low/moderate/high), assigning 50 participants to the control group and 50 participants to the intervention group. The intervention group will carry out a computerized cognitive stimulation intervention designed and adapted from occupational therapy according to the level of cognitive reserve, through the “stimulus” platform. The main result expected to be achieved is the improvement of higher brain functions. As secondary results, we expect that those cognitive aspects most vulnerable to aging will decrease more slowly (in areas such as memory, executive function, attention and processing speed), and that the cognitive reserve of the participants will increase, in addition to being able to balance gender differences in these aspects. We think that these results can have a positive impact on the creation of adapted, meaningful and stimulating CS programs in older adults to prevent MCI and experience healthier aging.

Abstract In this randomised, placebo-controlled trial, adults with impaired sleep (Pittsburgh Sleep Quality Index ≥ 5) were randomly assigned using a minimization algorithm to receive a formulation containing l-theanine plus lemon balm, valerian, and saffron extracts, or placebo, during 6 weeks. Objective sleep quality parameters were measured using an actigraphy device. We enrolled and randomised 64 individuals, 31 from the active group and 27 from the placebo group completed the 6 week follow-up. Mean sleep efficiency remained unmodified in the active group, and increased by 3% in the placebo group, the between-group difference in the change was not statistically significant (p = 0.49). Total sleep time also improved more with placebo (13.0 vs. 1.33 min, p = 0.66). Time wake after sleep onset (WASO) decreased more in the active group (4.6% vs. 2.4%), but the difference was not significant (p = 0.33). Mean PSQI decreased by 3.11 points (32.3%) in the active group, and by 3.86 points (39.5%) in the placebo group (p = 0.41). SF-36 increased more with placebo (+ 18.3 in active, + 32.1 in placebo, p = 0.68). Salivary cortisol remained unchanged in both groups. No serious adverse events were reported. Among adults with impaired sleep, a nutraceutical combination did not improve objective or subjective sleep parameters more than a placebo infusion.

Abstract A person with impaired emotion recognition is not able to correctly identify facial expressions represented by other individuals. The aim of the present study is to assess eyes gaze and facial emotion recognition in a healthy population using dynamic avatars in immersive virtual reality (IVR). For the first time, the viewing of each area of interest of the face in IVR is studied by gender and age. This work in healthy people is conducted to assess the future usefulness of IVR in patients with deficits in the recognition of facial expressions. Seventy-four healthy volunteers participated in the study. The materials used were a laptop computer, a game controller, and a head-mounted display. Dynamic virtual faces randomly representing the six basic emotions plus neutral expression were used as stimuli. After the virtual human represented an emotion, a response panel was displayed with the seven possible options. Besides storing the hits and misses, the software program internally divided the faces into different areas of interest (AOIs) and recorded how long participants looked at each AOI. As regards the overall accuracy of the participants’ responses, hits decreased from the youngest to the middle-aged and older adults. Also, all three groups spent the highest percentage of time looking at the eyes, but younger adults had the highest percentage. It is also noteworthy that attention to the face compared to the background decreased with age. Moreover, the hits between women and men were remarkably similar and, in fact, there were no statistically significant differences between them. In general, men paid more attention to the eyes than women, but women paid more attention to the forehead and mouth. In contrast to previous work, our study indicates that there are no differences between men and women in facial emotion recognition. Moreover, in line with previous work, the percentage of face viewing time for younger adults is higher than for older adults. However, contrary to earlier studies, older adults look more at the eyes than at the mouth.Consistent with other studies, the eyes are the AOI with the highest percentage of viewing time. For men the most viewed AOI is the eyes for all emotions in both hits and misses. Women look more at the eyes for all emotions, except for joy, fear, and anger on hits. On misses, they look more into the eyes for almost all emotions except surprise and fear.

Background: During the COVID-19 pandemic, weight loss programs rapidly transitioned to a virtual model, replacing in-person clinic visits. We sought to compare the observed weight loss and adherence to treatment between patients referred for intensive behavioral therapy (IBT) who were treated via telemedicine and those treated in person. Methods: After IRB approval, we conducted a retrospective observational study of patients referred for clinical bariatric IBT between January 2019 and June 2021 who were followed in person or via telemedicine. The primary endpoint was the percentage of excess BMI loss (EBL%); secondary endpoints included treatment adherence, duration of follow-up, and number of completed visits. Results: During the study period, 139 patients were seen for at least one IBT session for weight management: 62 were followed up in person (IP) and 77 via telemedicine (TM). The mean age, baseline BMI, and follow-up duration between the groups were similar. In the IP and TM groups, the EBL% was −24.7 ± 24.7 and −22.7 ± 19.5 (P = 0.989) and loss to follow-up after the first visit was 27.4% and 19.5% (P = 0.269), respectively. Conclusion: For the management of obesity, weight loss programs delivered via telemedicine can achieve similar outcomes to those provided via classical in-person visits. This study suggests that the integration of telecare into clinical practice in bariatric medicine should be considered in the future. Emerging technologies may allow adequate patient follow-up in multiple scenarios, specifically non-critical chronic disorders, and bring unanticipated benefits for patients and healthcare providers.

Introducción: los glucocorticoides (GC) han sido ampliamente utilizados en el tratamiento de patologías oculares debido a sus efectos antiinflamatorios y anti-angiogénicos. Se ha sugerido que el mecanismo de acción antiangiogénico de los GC puede estar relacionado con la enzima fosfatidilinositol-3-cinasa (PI3K), la cual desempeña un papel crucial en la angiogénesis mediada por el receptor nicotínico de acetilcolina alfa 7 (α7-nAChR). La PI3K es una enzima lipoproteica heterodimérica compuesta por las subunidades; reguladora (p85) y catalítica (p110). Objetivo: esta revisión examina la evidencia de la interrelación entre los GC, y la vía de señalización de PI3K activada por α7-nAChR en la angiogénesis “in vitro”. Metodología: se realizó una revisión bibliográfica utilizando los motores de búsqueda PubMed y Web of Science, relacionando los conceptos “endothelial cell”, “α7-nAChR”, “PI3K”, y “glucocorticoid”. Resultados: se seleccionaron 30 artículos que informaron sobre la expresión de α7-nAChR y PI3K en células endoteliales humanas. Además, del efecto de dexametasona sobre las subunidades de PI3K y Akt en modelos humano, murino y porcino. A partir de estos hallazgos, se propuso un mecanismo mediante el cual los GC ejercen su efecto antiangiogénico a través de la modulación en la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR en células endoteliales humanas. Conclusión: los antecedentes evidencian que dexametasona, ejerce su mecanismo de acción anti-angiogénico mediante el incremento de la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR. Estos hallazgos podrían contribuir a explicar la posible falla terapéutica en el área oftalmológica en pacientes fumadores.

Abstract The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and infection management. The aim of this study was to assess the dual IFN-γ and IL-2 detection, using a SARS-CoV-2 specific fluorescence ELISPOT, in patients undergoing acute disease, during convalescence, and after vaccination. We also evaluated humoral response and compared with T-cells with the aim of correlating both types of responses, and increase the number of specific response detection. Blood samples were drawn from acute COVID-19 patients and convalescent individuals classified according to disease severity; and from unvaccinated and vaccinated uninfected individuals. IgGs against Spike and nucleocapsid, IgMs against nucleocapsid, and neutralizing antibodies were also analyzed. Our results show that IFN-γ in combination with IL-2 increases response detection in acute and convalescent individuals (p = 0.023). In addition, IFN-γ detection can be a useful biomarker for monitoring severe acute patients, as our results indicate that those individuals with a poor outcome have lower levels of this cytokine. In some cases, the lack of cellular immunity is compensated by antibodies, confirming the role of both types of immune responses in infection, and confirming that their dual detection can increase the number of specific response detections. In summary, IFN-γ/IL-2 dual detection is promising for characterizing and assessing the immunization status, and helping in the patient management.

Abstract Background Medical education has evolved based on the application of pedagogical actions that place the student as the protagonist of the learning process through the use of active teaching methodologies. Within this context, higher education teachers should use strategies that focus on the student and his/her context and avoid traditional teaching methods. Specifically in medical schools, there is an even greater challenge since the teaching methods of medical curricula differ from those used in previous schooling. Consequently, students acquire their own style of processing information that is often incompatible with the profile of medical schools. This may be one of the factors responsible for the lack of motivation among undergraduates. Objective The aim of this study was to characterize the learning styles of students enrolled in a Brazilian medical school using the Felder-Soloman Index of Learning Styles (ILS). Methods This was a cross-sectional, descriptive, quantitative study that included students from the 1st to the 6th year of a Brazilian medical school. The students participating in this study voluntarily answered 44 questions about learning styles of the Felder-Silverman instrument validated in Brazil. The instrument was divided so that each domain consisted of 11 questions with two response options in which only one could be selected. For each domain, a score (1 point) was assigned to the selected option (a, b) of the question and the learning style category was determined as the difference between these values. For data collection and tabulation, we used the Learning Syle Platform (EdA Platform) developed based on Felder’s studies since this system processes information about the dimension analyzed, the preferred style, and the most striking characteristics of each style. Results The results showed that sensing was the preferred learning style of the students, followed by the sequential and visual styles. It was not possible to determine whether gender or age influences the choice of learning methods because of the homogeneity of the results. Conclusions The present data will enable teachers of the institution involved in this study to plan pedagogical actions that improve the students’ self-awareness, as well as their teaching-learning skills, by choosing the most adequate active methodologies for the medical education programs considering the individuality of each student and class.

Despite vaccination programs, pertussis has been poorly controlled, especially among older adults in Australia. This longitudinal, retrospective, observational study aimed to estimate the incidence and risk factors of pertussis among persons ≥50 years of age in Australia in the primary care setting, including those with underlying chronic obstructive pulmonary disease (COPD) or asthma. We used the IQVIA general practitioner electronic medical record database to identify patients ≥50 years of age with a clinical diagnosis of pertussis during 2015–2019. Pertussis incidence rates ranged from 57.6 to 91.4 per 100,000 persons and were higher among women and highest in those 50–64 years of age. Patients with COPD or asthma had higher incidence rates and an increased risk for pertussis compared with the overall population ≥50 years of age. Our findings suggest that persons ≥50 years of age in Australia with COPD or asthma have a higher incidence of and risk for pertussis diagnosis.

Abstract Microorganisms are ubiquitously distributed in nature and usually appear as biofilms attached to a variety of surfaces. Here, we report the development of a thick biofilm in the drain pipe of several standard laboratory ice machines, and we describe and characterise, through culture-dependent and -independent techniques, the composition of this oligotrophic microbial community. By using culturomics, 25 different microbial strains were isolated and taxonomically identified. The 16S rRNA high-throughput sequencing analysis revealed that Bacteroidota and Proteobacteria were the most abundant bacterial phyla in the sample, followed by Acidobacteriota and Planctomycetota, while ITS high-throughput sequencing uncovered the fungal community was clearly dominated by the presence of a yet-unidentified genus from the Didymellaceae family. Alpha and beta diversity comparisons of the ice machine microbial community against that of other similar cold oligotrophic and/or artificial environments revealed a low similarity between samples, highlighting the ice machine could be considered a cold and oligotrophic niche with a unique selective pressure for colonisation of particular microorganisms. The recovery and analysis of high-quality metagenome-assembled genomes (MAGs) yielded a strikingly high rate of new species. The functional profiling of the metagenome sequences uncovered the presence of proteins involved in extracellular polymeric substance (EPS) and fimbriae biosynthesis and also allowed us to detect the key proteins involved in the cold adaptation mechanisms and oligotrophic metabolic pathways. The metabolic functions in the recovered MAGs confirmed that all MAGs have the genes involved in psychrophilic protein biosynthesis. In addition, the highest number of genes for EPS biosynthesis was presented in MAGs associated with the genus Sphingomonas, which was also recovered by culture-based method. Further, the MAGs with the highest potential gene number for oligotrophic protein production were closely affiliated with the genera Chryseoglobus and Mycobacterium. Our results reveal the surprising potential of a cold oligotrophic microecosystem within a machine as a source of new microbial taxa and provide the scientific community with clues about which microorganisms are able to colonise this ecological niche and what physiological mechanisms they develop. These results pave the way to understand how and why certain microorganisms can colonise similar anthropogenic environments.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Background: Introduction: Prehabilitation in the field of oncology has been defined as “the process in the continuum of care that occurs between diagnosis and the start of treatment involving physical and psychological measures that determine the patient’s baseline functional status.” Aim: To determine the effectiveness of a Prehabilitation consultation on self-care and targeted physical exercise for patients diagnosed with abdominopelvic cancer. Design: An observational study that will evaluate the pre-post efficacy of an ad-hoc designed Prehabilitation intervention. The study population consists of patients diagnosed with colon or gynecological cancer with a surgical indication as part of their therapeutic plan from the General Surgery Services. It is configured around four key interventions: (a) health education and self-care, (b) specific nutritional counseling, (c) initial psychological assessment, and (d) directed physical exercise intervention. Health education, self-care interventions, and physical exercise will be carried out weekly from diagnosis to the scheduled surgery day. Results: Aspects such as self-care capacity or agency, perioperative anxiety, aerobic capacity, strength and flexibility, postoperative complications, and recovery time to adjuvant treatment will be measured using tools such as Appraisal of self-care agency scale (ASA), State Trait Anxiety Inventory (STAI), walking test, sit and Reach, Hand Grip or Squad Jump. Conclusion: Utilizing validated tools for analyzing selected variables will contribute to refining and expanding care guidelines, ultimately enhancing support for both patients and their caregivers.

Abstract Palaeogenomics is contributing to refine our understanding of many major evolutionary events at an unprecedented resolution, with relevant impacts in several fields, including phylogenetics of extinct species. Few extant and extinct animal species from Mediterranean regions have been characterised at the DNA level thus far. The Sardinian pika, Prolagus sardus (Wagner, 1829), was an iconic lagomorph species that populated Sardinia and Corsica and became extinct during the Holocene. There is a certain scientific debate on the phylogenetic assignment of the extinct genus Prolagus to the family Ochotonidae (one of the only two extant families of the order Lagomorpha) or to a separated family Prolagidae, or to the subfamily Prolaginae within the family Ochotonidae. In this study, we successfully reconstructed a portion of the mitogenome of a Sardinian pika dated to the Neolithic period and recovered from the Cabaddaris cave, an archaeological site in Sardinia. Our calibrated phylogeny may support the hypothesis that the genus Prolagus is an independent sister group to the family Ochotonidae that diverged from the Ochotona genus lineage about 30 million years ago. These results may contribute to refine the phylogenetic interpretation of the morphological peculiarities of the Prolagus genus already described by palaeontological studies.

Abstract The Neolithic burial of Grotta di Pietra Sant’Angelo (CS) represents a unique archaeological finding for the prehistory of Southern Italy. The unusual placement of the inhumation at a rather high altitude and far from inhabited areas, the lack of funerary equipment and the prone deposition of the body find limited similarities in coeval Italian sites. These elements have prompted wider questions on mortuary customs during the prehistory of Southern Italy. This atypical case requires an interdisciplinary approach aimed to build an integrated bioarchaeological profile of the individual. The paleopathological investigation of the skeletal remains revealed the presence of numerous markers that could be associated with craft activities, suggesting possible interpretations of the individual’s lifestyle. CT analyses, carried out on the maxillary bones, showed the presence of a peculiar type of dental wear, but also a good density of the bone matrix. Biomolecular and micromorphological analyses of dental calculus highlight the presence of a rich Neolithic-like oral microbiome, the composition of which is consistent with the presence pathologies. Finally, paleogenomic data obtained from the individual were compared with ancient and modern Mediterranean populations, including unpublished high-resolution genome-wide data for 20 modern inhabitants of the nearby village of San Lorenzo Bellizzi, which provided interesting insights into the biodemographic landscape of the Neolithic in Southern Italy.

Placerias hesternus, a Late Triassic dicynodont, is one of the last megafaunal synapsids of the Mesozoic. The species has a tusk-like projection on its maxillary bone, known as the caniniform process. This process has been hypothesized to be sexually dimorphic since the 1950s, however this claim has not been thoroughly investigated quantitatively. Here, we examined maxillae, premaxillae, quadrates, and fibulae from a single population from the Placerias Quarry in the Blue Mesa Member of the Chinle Formation, near St. Johns, Arizona, USA to determine if the caniniform process is dimorphic. We made a total of 25 measurements from the four bones and used a maximum likelihood framework to compare the fit of unimodal versus bimodal distributions for each set of measurements. Our results from complete maxillae reveal that the caniniform process has two distinct morphs, with a shorter and longer form. This interpretation is substantiated both by strong statistical support for bimodal distribution of caniniform lengths, and by clustering analysis that clearly distinguishes two morphs for the maxillae. Clustering analysis also shows support for potential dimorphism in the shape of the quadrate. However, no measurements from elements other than the maxilla have a strong likelihood of bimodal distribution. These results support the long-standing hypothesis that the caniniform in Placerias was dimorphic. Alternative explanations to sexual dimorphism that could account for the dimorphism among these fossils include the presence of juveniles in the sample or time-averaged sampling of a chronospecies, but both have been previously rejected for the Placerias Quarry population. The lack of strong dimorphism in non-maxilla elements and increased variation in caniniform length of the large-caniniform morph suggest that the caniniform is a secondary sexual trait, possibly used in intraspecific competition.

Background: The global population is experiencing accelerated biopsychosocial aging. Cognitive impairment is frequently associated with functional impairment in basic and instrumental daily living activities. To maintain optimal cognitive and functional functioning, health professionals recommend that older adults participate in cognitive training. Aims: This study examines the cognitive and functional evolution of older adults with and without Intellectual Disability and the factors associated with favourable evolution following the intervention of a multicomponent programme based on the human occupational model and the person-centred care model. Methods and procedures: 247 people participated. Descriptive and univariate analyses were performed to examine baseline data. The Wilcoxon paired samples test was used to compare cognitive and functional evolution one year after the intervention. Linear regression was used to detect factors predicting favourable evolution. Outcomes and results: Both populations improved cognitively. There was no change in basic activities of daily living. There was an improvement in instrumental activities of daily living in the group with Intellectual Disability. None of the variables collected was a predictor of greater improvement. Conclusions and implications: This study demonstrated that older people with Intellectual Disability who have supports to cope with this life stage can improve their cognitive and functional abilities.

Este artículo aborda la relevancia del aprendizaje significativo en la educación, destacando la perspectiva teórica de Ausubel (1978) que surge en los años setenta. A pesar de no ser una corriente reciente, la implementación de este enfoque no es habitual, y los docentes universitarios continúan utilizando métodos mecánicos y repetitivos que relegan al estudiante a un papel pasivo. Todo ello a pesar de que en el ámbito de las ciencias de la salud se enfatiza la necesidad de cambiar paradigmas en la enseñanza y aprendizaje, y reconocer que los nuevos aprendizajes se generan en contextos significativos y se conectan con los saberes previos de los estudiantes. Motivados por esta premisa, el equipo de autores realizó una investigación para indagar sobre el concepto y la aplicabilidad que un grupo de estudiantes de máster en Educación Médica otorgan al aprendizaje significativo. La metodología empleada incluyó una encuesta con preguntas abiertas para comprender el alcance y la aplicabilidad de este concepto en la práctica clínica docente, mediante un enfoque de investigación cualitativa, utilizando una encuesta de preguntas abiertas sobre la escasa implementación del aprendizaje significativo, los antecedentes sobre la prevalencia de métodos transmisionistas así como la percepción y aplicación de este enfoque. Los resultados destacan la resistencia a la implementación del aprendizaje significativo, evidenciando la prevalencia de métodos tradicionales. Se presentan cifras cuantitativas que respaldan estas observaciones, subrayando la necesidad de un cambio en las prácticas docentes. Este estudio propone soluciones para fomentar el aprendizaje significativo en la educación médica y destaca las implicaciones y aplicaciones de los resultados en la práctica clínica docente.

Abstract For endocrine-positive Her2 negative breast cancer patients at an early stage, the benefit of adding chemotherapy to adjuvant endocrine therapy is not still confirmed. Several genomic tests are available on the market but are very expensive. Therefore, there is the urgent need to explore novel reliable and less expensive prognostic tools in this setting. In this paper, we shown a machine learning survival model to estimate Invasive Disease-Free Events trained on clinical and histological data commonly collected in clinical practice. We collected clinical and cytohistological outcomes of 145 patients referred to Istituto Tumori “Giovanni Paolo II”. Three machine learning survival models are compared with the Cox proportional hazards regression according to time-dependent performance metrics evaluated in cross-validation. The c-index at 10 years obtained by random survival forest, gradient boosting, and component-wise gradient boosting is stabled with or without feature selection at approximately 0.68 in average respect to 0.57 obtained to Cox model. Moreover, machine learning survival models have accurately discriminated low- and high-risk patients, and so a large group which can be spared additional chemotherapy to hormone therapy. The preliminary results obtained by including only clinical determinants are encouraging. The integrated use of data already collected in clinical practice for routine diagnostic investigations, if properly analyzed, can reduce time and costs of the genomic tests.

Abstract Endophytic fungi have been demonstrated to produce bioactive secondary metabolites, some of which promote plant growth. Three endophytic fungi isolated from healthy plants living in dehesas of Extremadura (Spain) were identified and evaluated for their ability to produce phytohormone-like substances, antioxidant activity, total polyphenol content, phosphate solubilization ability and siderophore and ammonia production. The filtrates and extracts produced by the three endophytes were applied to Lolium multiflorum seeds and seedlings under both in vitro and greenhouse conditions, to analyse their influence on plant growth traits such as germination, vigour index, chlorophyll data, number and length of leaves and roots, and dry weight. All three endophytes, which were identified as Fusarium avenaceum, Sarocladium terricola and Xylariaceae sp., increased the germination of L. multiflorum seeds by more than 70%. Shoot and root length, plant dry weight and the number of roots were positively affected by the application of fungal filtrates and/or extracts, compared with controls. The tentative HPLC–MS identification of phytohormone-like substances, such as gibberellin A2 and zeatin, or the antioxidant acetyl eugenol, may partially explain the mechanisms of L. multiflorum plant growth promotion after the application of fungal filtrates and/or extracts.

Abstract Retrospective perceptions of parental bonding may be a protective factor for emotional health. These perceptions are grounded in autobiographical memory, which plays a key role in the onset and maintenance of depressive symptomatology. The aim of the present study was to explore whether the emotional valence of autobiographical memories (positive and negative) and the dimensions of parental bonding (care and protection) have an impact on depressive symptomatology, examining the role of depressive rumination and possible age-related differences. A total of 139 young adults (18–28 years) and 124 older adults (65–88 years) completed the Parental Bonding Instrument, the Beck Depression Inventory (BDI-II), the Autobiographical Memory Test and the Short Depressive Rumination Scale. Our results show that positive autobiographical memories serve as a protective factor for depressive symptoms in both young and older adults. Additionally, in young adults, high paternal care and protection scores are associated with increased negative autobiographical memories, although this association has no effect on depressive symptomatology. In older adults, high maternal protection scores are directly related to greater depressive symptomatology. Depressive rumination significantly increases depressive symptoms in both young and older adults, with an increase in negative autobiographical memories in young adults, and a decrease in such memories in older adults. Our findings progress the understanding of the relationships between parental bonding and autobiographical memory with respect to emotional disorders, which, in turn, will help in the design of effective prevention measures.

Abstract Improving the cellular capacity of Chinese hamster ovary (CHO) cells to produce large amounts of therapeutic proteins remains a major challenge for the biopharmaceutical industry. In previous studies, we observed strong correlations between the performance of CHO cells and expression of two transcription factors (TFs), MYC and XBP1s. Here, we have evaluated the effective of overexpression of these two TFs on CHO cell productivity. To address this goal, we generated an EPO-producing cell line (CHOEPO) using a targeted integration approach, and subsequently engineered it to co-overexpress MYC and XBP1s (a cell line referred to as CHOCXEPO). Cells overexpressing MYC and XBP1s increased simultaneously viable cell densities and EPO production, leading to an enhanced overall performance in cultures. These improvements resulted from the individual effect of each TF in the cell behaviour (i.e., MYC-growth and XBP1s-productivity). An evaluation of the CHOCXEPO cells under different environmental conditions (temperature and media glucose concentration) indicated that CHOCXEPO cells increased cell productivity in high glucose concentration. This study showed the potential of combining TF-based cell engineering and process optimisation for increasing CHO cell productivity.

Abstract Respiratory viral infections (RVIs) are frequent in preterm infants possibly inducing long-term impact on respiratory morbidity. Immune response and respiratory barriers are key defense elements against viral insults in premature infants admitted to Neonatal Intensive Care Units (NICUs). Our main goals were to describe the local immune response in respiratory secretions of preterm infants with RVIs during NICU admission and to evaluate the expression and synthesis of lung barrier regulators, both in respiratory samples and in vitro models. Samples from preterm infants that went on to develop RVIs had lower filaggrin gene and protein levels at a cellular level were compared to never-infected neonates (controls). Filaggrin, MIP-1α/CCL3 and MCP-1 levels were higher in pre-infection supernatants compared to controls. Filaggrin, HIF-1α, VEGF, RANTES/CCL5, IL-17A, IL-1β, MIP-1α and MIP-1β/CCL5 levels were higher during and after infection. ROC curve and logistic regression analysis shows that these molecules could be used as infection risk biomarkers. Small airway epithelial cells stimulated by poly:IC presented reduced filaggrin gene expression and increased levels in supernatant. We conclude that filaggrin gene and protein dysregulation is a risk factor of RVI in newborns admitted at the NICU.

Abstract Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard ( https://sarsaigua.icra.cat ). After 20 months of monitoring (July 20–March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.

Introduction Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population.Methods and analysis This is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185

BackgroundTraditional surveillance systems rely on routine collection of data. The inherent delay in retrieval and analysis of data leads to reactionary rather than preventive measures. Forecasting and analysis of behavior-related data can supplement the information from traditional surveillance systems. ObjectiveWe assessed the use of behavioral indicators, such as the general public’s interest in the risk of contracting SARS-CoV-2 and changes in their mobility, in building a vector autoregression model for forecasting and analysis of the relationships of these indicators with the number of COVID-19 cases in the National Capital Region. MethodsAn etiologic, time-trend, ecologic study design was used to forecast the daily number of cases in 3 periods during the resurgence of COVID-19. We determined the lag length by combining knowledge on the epidemiology of SARS-CoV-2 and information criteria measures. We fitted 2 models to the training data set and computed their out-of-sample forecasts. Model 1 contains changes in mobility and number of cases with a dummy variable for the day of the week, while model 2 also includes the general public’s interest. The forecast accuracy of the models was compared using mean absolute percentage error. Granger causality test was performed to determine whether changes in mobility and public’s interest improved the prediction of cases. We tested the assumptions of the model through the Augmented Dickey-Fuller test, Lagrange multiplier test, and assessment of the moduli of eigenvalues. ResultsA vector autoregression (8) model was fitted to the training data as the information criteria measures suggest the appropriateness of 8. Both models generated forecasts with similar trends to the actual number of cases during the forecast period of August 11-18 and September 15-22. However, the difference in the performance of the 2 models became substantial from January 28 to February 4, as the accuracy of model 2 remained within reasonable limits (mean absolute percentage error [MAPE]=21.4%) while model 1 became inaccurate (MAPE=74.2%). The results of the Granger causality test suggest that the relationship of public interest with number of cases changed over time. During the forecast period of August 11-18, only change in mobility (P=.002) improved the forecasting of cases, while public interest was also found to Granger-cause the number of cases during September 15-22 (P=.001) and January 28 to February 4 (P=.003). ConclusionsTo the best of our knowledge, this is the first study that forecasted the number of COVID-19 cases and explored the relationship of behavioral indicators with the number of COVID-19 cases in the Philippines. The resemblance of the forecasts from model 2 with the actual data suggests its potential in providing information about future contingencies. Granger causality also implies the importance of examining changes in mobility and public interest for surveillance purposes.

A recent study published data on the growth performance, relative weights of the organs of the gastrointestinal tract, liver histology, serum biochemistry, and hematological parameters for turkey poults fed an experimental diet contaminated with aflatoxin B1 (AFB1) and humic acids (HA) extracted from vermicompost. The negative effects of AFB1 (250 ng AFB1/g of feed) were significantly reduced by HA supplementation (0.25% w/w), suggesting that HA might be utilized to ameliorate the negative impact of AFB1 from contaminated diets. The present study shows the results of the remaining variables, as an extension of a previously published work which aimed to evaluate the impact of HA on the intestinal microbiota, gut integrity, ileum morphometry, and cellular immunity of turkey poults fed an AFB1-contaminated diet. For this objective, five equal groups of 1-day-old female Nicholas-700 turkey poults were randomly assigned to the following treatments: negative control (basal diet), positive control (basal diet + 250 ng AFB1/g), HA (basal diet + 0.25% HA), HA + AFB1 (basal diet + 0.25% HA + 250 ng AFB1/g), and Zeolite (basal diet + 0.25% zeolite + 250 ng AFB1/g). In the experiment, seven replicates of ten poults each were used per treatment (n = 70). In general, HA supplementation with or without the presence of AFB1 showed a significant increase (p < 0.05) in the number of beneficial butyric acid producers, ileum villi height, and ileum total area, and a significant reduction in serum levels of fluorescein isothiocyanate–dextran (FITC-d), a marker of intestinal integrity. In contrast, poults fed with AFB1 showed a significant increase in Proteobacteria and lower numbers of beneficial bacteria, clearly suggesting gut dysbacteriosis. Moreover, poults supplemented with AFB1 displayed the lowest morphometric parameters and the highest intestinal permeability. Furthermore, poults in the negative and positive control treatments had the lowest cutaneous basophil hypersensitivity response. These findings suggest that HA supplementation enhanced intestinal integrity (shape and permeability), cellular immune response, and healthier gut microbiota composition, even in the presence of dietary exposure to AFB1. These results complement those of the previously published study, suggesting that HA may be a viable dietary intervention to improve gut health and immunity in turkey poults during aflatoxicosis.

Abstract A simple, rapid procedure is required for the routine detection and quantification of haemolysis, one of the main sources of unreliable results in serum analysis. In this study, we compared two different approaches for the rapid determination of haemolysis in cattle serum. The first consisted of estimating haemolysis via a simple direct ultraviolet–visible (UV–VIS) spectrophotometric measurement of serum samples. The second involved analysis of red, green, blue (RGB) colour data extracted from digital images of serum samples and relating the haemoglobin (Hb) content by means of both univariate (R, G, B and intensity separately) and multivariate calibrations (R, G, B and intensity jointly) using partial least squares regression and artificial neural networks. The direct UV–VIS analysis and RGB-multivariate analysis using neural network methods were both appropriate for evaluating haemolysis in serum cattle samples. The procedures displayed good accuracy (mean recoveries of 100.7 and 102.1%, respectively), adequate precision (with coefficients of variation from 0.21 to 2.68%), limit of detection (0.14 and 0.21 g L–1, respectively), and linearity of up to 10 g L–1.

Background/Aims Tight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn’s disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD. Methods Patients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used. Results One hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P

Male researchers dominate scientific production in science, technology, engineering, and mathematics (STEM). However, potential mechanisms to avoid this gender imbalance remain poorly explored in STEM, including ecology and evolution areas. In the last decades, changes in the peer-review process towards double-anonymized (DA) have increased among ecology and evolution (EcoEvo) journals. Using comprehensive data on articles from 18 selected EcoEvo journals with an impact factor >1, we tested the effect of the DA peer-review process in female-leading (i.e., first and senior authors) articles. We tested whether the representation of female-leading authors differs between double and single-anonymized (SA) peer-reviewed journals. Also, we tested if the adoption of the DA by previous SA journals has increased the representativeness of female-leading authors over time. We found that publications led by female authors did not differ between DA and SA journals. Moreover, female-leading articles did not increase after changes from SA to DA peer-review. Tackling female underrepresentation in science is a complex task requiring many interventions. Still, our results highlight that adopting the DA peer-review system alone could be insufficient in fostering gender equality in EcoEvo scientific publications. Ecologists and evolutionists understand how diversity is important to ecosystems’ resilience in facing environmental changes. The question remaining is: why is it so difficult to promote and keep this “diversity” in addition to equity and inclusion in the academic environment? We thus argue that all scientists, mentors, and research centers must be engaged in promoting solutions to gender bias by fostering diversity, inclusion, and affirmative measures.

Introducción: La pandemia por la COVID-19 ocasionó una serie de repercusiones y cambios drásticos en la salud mental de los estudiantes de pregrado, como el cansancio emocional, lo cual pudo su bienestar psicológico. Objetivo: Determinar si existe relación entre el cansancio emocional y el bienestar psicológico de los estudiantes de la carrera profesional de enfermería. Método: El enfoque fue cuantitativo, el diseño no experimental y el tipo, descriptivo-correlacional de corte transversal. La muestra estuvo conformada por 184 estudiantes a quienes se les aplicó la Escala de Cansancio Emocional y la Escala de Bienestar Psicológico para Adultos, instrumentos adaptados para estudiantes y con adecuados niveles de validez basada en el contenido y confiabilidad. Para identificar la relación entre las variables de estudio se aplicó el coeficiente de correlación de Pearson. Resultados: El 63 % de los estudiantes evidenciaron niveles moderados de cansancio emocional y el 75 % tuvieron altos niveles de bienestar psicológico. Por otro lado, se observó una correlación inversa entre las variables cansancio emocional y bienestar psicológico (r= -0,267; p< 0,05). Asimismo, se encontró que las mujeres presentaron mayores niveles de cansancio emocional que los varones. Conclusiones: Existe relación inversa y significativa entre el cansancio emocional y el bienestar psicológico de los estudiantes de Enfermería durante la pospandemia.

Abstract In breast cancer patients, an accurate detection of the axillary lymph node metastasis status is essential for reducing distant metastasis occurrence probabilities. In case of patients resulted negative at both clinical and instrumental examination, the nodal status is commonly evaluated performing the sentinel lymph-node biopsy, that is a time-consuming and expensive intraoperative procedure for the sentinel lymph-node (SLN) status assessment. The aim of this study was to predict the nodal status of 142 clinically negative breast cancer patients by means of both clinical and radiomic features extracted from primary breast tumor ultrasound images acquired at diagnosis. First, different regions of interest (ROIs) were segmented and a radiomic analysis was performed on each ROI. Then, clinical and radiomic features were evaluated separately developing two different machine learning models based on an SVM classifier. Finally, their predictive power was estimated jointly implementing a soft voting technique. The experimental results showed that the model obtained by combining clinical and radiomic features provided the best performances, achieving an AUC value of 88.6%, an accuracy of 82.1%, a sensitivity of 100% and a specificity of 78.2%. The proposed model represents a promising non-invasive procedure for the SLN status prediction in clinically negative patients.

Abstract Objective The advent of new techniques such as video-assisted thoracoscopic surgery (VATS) for the removal of lung segments leads to compression of the surgical specimen, with the possible dissemination of neoplastic cells. The sheer volume of surgeries performed using these techniques has caused many institutions to stop removing the surgical specimen using an endobag, even when retractors/protectors are used in the instrumentalization incision. This study aimed to collect data from patients undergoing lung resection by VATS and analyze the cytopathological results of the collected material. Results A total of 47 endobag fluid samples were collected from patients who underwent VATS. The surgical specimen was subjected to histopathological analysis, and all patients underwent pathological TNM staging. In the cytopathological analyses, only 2 (4.3%) specimens of endobag fluid aspirate were positive for neoplastic cells. In these two cases, the tumors were peripheral, both with diagnoses of moderately differentiated adenocarcinoma and with classifications of T1bN0M0 and T3N0M0. These results indicate that although there is a low incidence of tumor cells in endobag fluid, it is always better to perform surgery using all available protective measures to avoid tumor implantation in the thoracic cavity to the greatest extent possible.

Covid-19 outbreak led all organizations to reorganize their processes to prevent infection and contagion risk. All healthcare facilities, included penitentiary mental health services, had to redesign their processes to safely deliver care services. In this paper, the case of a Penitentiary Mental Health Division located in southern Italy is presented. Soft System Methodology and Business process management principles and techniques are adopted to analyse and redesign the detainees' mental health care process. The process, characterized by direct, close and prolonged contact with patients, exposes detainees and healthcare staff to a high Covid-19 infection risk. Through document analysis, interviews with the actors involved in the process and direct observation, the process's inefficiencies and criticalities are identified. The process is redesigned to make it compliant with Covid-19 prevention provisions and national penitentiary regulations and address the other criticalities. The proposed methodological approach-which innovatively combines Soft System Methodology and Business Process Management-constitutes a human-centered process-based redesign approach that can be used both in healthcare and other organizational settings.

BackgroundIntra-abdominal hypertension and abdominal compartment syndrome are common with clinically significant consequences. We investigated the pathophysiological effects of raised IAP as part of a more extensive exploratory animal study. The study design included both pneumoperitoneum and mechanical intestinal obstruction models.MethodsForty-nine female swine were divided into six groups: a control group (Cr; n = 5), three pneumoperitoneum groups with IAPs of 20mmHg (Pn20; n = 10), 30mmHg (Pn30; n = 10), 40mmHg (Pn40; n = 10), and two mechanical intestinal occlusion groups with IAPs of 20mmHg (MIO20; n = 9) and 30mmHg (MIO30; n = 5).ResultsThere were significant changes (pConclusionsThis study identified and quantified the impact of intra-abdominal hypertension at different pressures on several organ systems and highlighted the significance of even short-lived elevations. Two models of intra-abdominal pressure were used, with a mechanical obstruction model showing more rapid changes in metabolic and haematological changes. These may represent different underlying cellular and vascular pathophysiological processes, but this remains unclear.

BackgroundChronic pain is a common complaint having distressing consequences for those that suffer from it. Pain and depression concur within the context of comorbidity, and both share underlying stress conditions. Sense of coherence (SOC) is a factor that determines how well an individual manages stress and stays healthy. Its relationship with depression has been frequently reported in the literature. Our objective was to assess the amount of evidence available regarding the association between SOC and depression in patients suffering from chronic pain.MethodsA systematic review and meta-analysis were performed. Searches were conducted between November 01 and December 31, 2020 in PubMed, Web of Science, Embase, PsycINFO, Psicodoc, ScienceDirect and Dialnet. There were no restrictions regarding the date of publication of the study. Evidence related to the relationship between SOC and depression in patients with chronic pain was summarized and compared.ResultsA total of 163 articles were identified. We included 9 papers in the qualitative and quantitative synthesis. The pooled correlation coefficient was -0.55 (95%: -0.70; -0.41) and was not modified after removing any study. The heterogeneity across the studies was considerable (I2 = 94.8%; p < 0.001). The random-effects meta-regression models for the association between SOC and depression showed that age (p = 0.148) and percentage of women (p = 0.307) were not related to heterogeneity across studies. No publication bias was detected (p = 0.720).ConclusionsAt first glance, the included studies give the impression that SOC is an important factor in depression levels of patients with chronic pain. Most of the included studies revealed a moderate association between SOC and depressive symptoms.

BackgroundRhodnius prolixus is a vector of Chagas disease and has become a model organism to study physiology, behavior, and pathogen interaction. The publication of its genome allowed initiating a process of comparative characterization of the gene expression profiles of diverse organs exposed to varying conditions. Brain processes control the expression of behavior and, as such, mediate immediate adjustment to a changing environment, allowing organisms to maximize their chances to survive and reproduce. The expression of fundamental behavioral processes like feeding requires fine control in triatomines because they obtain their blood meals from potential predators. Therefore, the characterization of gene expression profiles of key components modulating behavior in brain processes, like those of neuropeptide precursors and their receptors, seems fundamental. Here we study global gene expression profiles in the brain of starved R. prolixus fifth instar nymphs by means of RNA sequencing (RNA-Seq).ResultsThe expression of neuromodulatory genes such as those of precursors of neuropeptides, neurohormones, and their receptors; as well as the enzymes involved in the biosynthesis and processing of neuropeptides and biogenic amines were fully characterized. Other important gene targets such as neurotransmitter receptors, nuclear receptors, clock genes, sensory receptors, and takeouts genes were identified and their gene expression analyzed.ConclusionWe propose that the set of neuromodulatory-related genes highly expressed in the brain of starved R. prolixus nymphs deserves functional characterization to allow the subsequent development of tools targeting them for bug control. As the brain is a complex structure that presents functionally specialized areas, future studies should focus on characterizing gene expression profiles in target areas, e.g. mushroom bodies, to complement our current knowledge.

The baculum of mammals offers the opportunity to study the reproductive biology of extinct species given that it is a fossilizable part of the male genitalia and that its size and shape correlate with several aspects of the reproductive biology of extant mammals. Fossil bacula, however, are rare. Currently, bacula have been described from only two extinct species of canids, one from the subfamily Caninae and the other from the extinct subfamily Hesperocyoninae. Here, I describe the bacula of five extinct species of Borophaginae, each of which was found with other skeletal elements that have enabled identification to the species level. Two specimens (Aelurodon ferox and Aelurodon stirtoni) are largely complete, while the baculum from Carpocyon compressus is complete but still embedded in matrix that obscures some of its features. The bacula of Paratomarctus euthos and Desmocyon thomsoni are incomplete, but they provide useful information nonetheless. These borophagine bacula are similar to extant canines in being robust, having a urethral groove, and a simple distal end. These features suggest that the Borophaginae had long-lasting copulation and possibly spontaneous ovulation, similar to the extant canines. However, unlike the straight baculum of extant canines, borophagine bacula are ventrally curved (arched), which is also observed in the hesperocyonine baculum. The implication of this curvature for the reproductive biology of these animals remains unknown.

Abstract Despite the increasing evidence of links between human gut and health, the number of gut microbiomes that have been studied to date at a country level are surprisingly low. Mediterranean countries, including some of the most long-lived and healthy countries in the world, have not been considered so far in those studies at a large scale. The main objective of this work is to characterize the gut microbiome of a healthy adult population of a Mediterranean, paradigmatically healthy country: Spain. Stool samples from 530 healthy volunteers were collected, total metagenomic DNA extracted, and the microbial profiles determined through 16S rRNA metataxonomic sequencing. Our results confirm the associations between several microbial markers and different variables, including sex, age, BMI and diet choices, and bring new insights into the relationship between microbiome and diet in the Spanish population. Remarkably, some of the associations found, such as the decrease of Faecalibacterium with age or the link of Flavonifractor with less healthy dietary habits, have been barely noticed in other large-scale cohorts. On the other hand, a range of links between microorganisms, diet, and lifestyle coincide with those reported in other populations, thus increasing the robustness of such associations and confirming the importance of these microbial markers across different countries. Overall, this study describes the Spanish “normal” microbiome, providing a solid baseline for future studies investigating the effects of gut microbiome composition and deviations in the adherence to the Mediterranean diet.

Cerebral nocardia infections is a rare entity, which has been mainly reported in immunosuppressed patients. Currently, there are no clinical guidelines for first-line treatment. Our case refers to an older immunocompetent adult, with encephalopathy and left hemiparesis, associated with lesions compatible with multiple brain abscess and suggestive of infectious etiology. He initially received treatment for tuberculosis, bacterial abscess, and toxoplasmosis, without a favorable clinical response. An empirical treatment for nocardiosis started, by using meropenem and trimethoprim / sulfamethoxazole, and clinical and imaging improvement was achieved. The occurrence of adverse events forces the temporary use of alternative medications. We highlight some criteria for including nocardiosis in the differential diagnosis in cases of multiple brain abscess and mention laboratory diagnostic methods and drugs to initiate empirical treatment.

Abstract Background Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence. Method Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained. Results Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies. Conclusions Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.

We retrospectively investigated mother-to-infant transmission of group B Streptococcus (GBS) in 98 cases of late-onset disease reported during 2007–2018 by a network in Italy. Mothers with full assessment of vaginal/rectal carriage tested at prenatal screening and at time of late onset (ATLO) were included. Thirty-three mothers (33.7%) were never GBS colonized; 65 (66.3%) were vaginal/rectal colonized, of which 36 (36.7%) were persistently colonized. Mothers with vaginal/rectal colonization ATLO had high rates of GBS bacteriuria (33.9%) and positive breast milk culture (27.5%). GBS strains from mother–infant pairs were serotype III and possessed the surface protein antigen Rib. All but 1 strain belonged to clonal complex 17. GBS strains from 4 mother–infant pairs were indistinguishable through pulsed-field gel electrophoresis. At least two thirds of late-onset cases are transmitted from mothers, who often have vaginal/rectal carriage, positive breast milk culture, or GBS bacteriuria, which suggests heavy maternal colonization.

Summary: Background: Adipose tissue is a source of multiple factors that modulate systemic insulin sensitivity and cardiovascular risk. Taurine is obtained from the diet but it is less known that it is endogenously synthesized by cysteine dioxygenase type 1 (CDO1). CDO1 exerts a role in adipose tissue from rodent models, but the potential translational value in humans is not available in the literature. Methods: CDO1 gene expression was analysed in visceral and subcutaneous adipose tissue samples in association with metabolic traits in participants with different degrees of obesity in four independent cohorts. CDO1 was also evaluated in isolated human adipocytes in vitro. Mechanistically, CDO1gene knockdown (KD) of human preadipocytes and adipose-derived mesenchymal stem cells (ASC52telo) (using lentiviral particles) was also evaluated. Mitochondrial respiratory function of adipocytes was evaluated using Seahorse. Findings: Both visceral (VAT) and subcutaneous adipose tissue (SAT) CDO1 mRNA was associated with gene expression markers of adipose tissue function in the four cohorts. Higher CDO1 expression was linked to decreased fasting triglycerides and blood HbA1c even after adjusting by age, BMI and sex. In addition, CDO1 mRNA positively correlated with the expression of genes involved in adipogenesis and negatively with different inflammatory markers. Both VAT and SAT CDO1 mRNA was mainly expressed in adipocytes and significantly increased during adipocyte differentiation, but attenuated under inflammatory conditions. Mechanistically, CDO1 gene KD reduced taurine biosynthesis, evidencing lower CDO1 activity. In both human preadipocytes and ASC52telo cells, CDO1 gene KD resulted in decreased gene expression markers of adipogenesis (ADIPOQ, FABP4, FASN, SLC2A4, CEBPA) and increased inflammatory genes (TNF and IL6) during adipocyte differentiation. Of note, CDO1 gene KD led to decreased mitochondrial respiratory function in parallel to decreased expression of mitochondrial function-, but not biogenesis-related genes. Interpretation: Current findings show the relevance of CDO1 in adipose tissue physiology, suggesting its contribution to an improved systemic metabolic profile. Funding: This work was partially supported by research grants PI16/01173, PI19/01712, PI20/01090 and PI21/01361 from the Instituto de Salud Carlos III from Spain, Fondo Europeo de Desarrollo Regional (FEDER) funds, and VII Spanish Diabetes Association grants to Basic Diabetes Research Projects led by young researchers.

Respiratory tract infections (RTIs) are one of the most common reasons for seeking healthcare, but are amongst the most challenging diseases in terms of clinical decision-making. Proper and timely diagnosis is critical in order to optimise management and prevent further emergence of antimicrobial resistance by misuse or overuse of antibiotics. Diagnostic tools for RTIs include those involving syndromic and aetiological diagnosis: from clinical and radiological features to laboratory methods targeting both pathogen detection and host biomarkers, as well as their combinations in terms of clinical algorithms. They also include tools for predicting severity and monitoring treatment response. Unprecedented milestones have been achieved in the context of the COVID-19 pandemic, involving the most recent applications of diagnostic technologies both at genotypic and phenotypic level, which have changed paradigms in infectious respiratory diseases in terms of why, how and where diagnostics are performed. The aim of this review is to discuss advances in diagnostic tools that impact clinical decision-making, surveillance and follow-up of RTIs and tuberculosis. If properly harnessed, recent advances in diagnostic technologies, including omics and digital transformation, emerge as an unprecedented opportunity to tackle ongoing and future epidemics while handling antimicrobial resistance from a One Health perspective.

Background: Porteirinha is endemic for visceral leishmaniasis (VL), with intense disease transmission of the disease. We evaluated the impact of canine euthanasia as a single control measure on the incidence of VL in humans and canines. Methods: A prospective observational cohort study was carried out over four years (1998–2002) in 8 of the 12 neighborhoods of the city. The dynamics of canine visceral leishmaniasis (CVL) transmission were evaluated for 2 years, before beginning the screening–culling intervention. The comparative morbidity index (CMI) was used to stratify areas with the greatest risk of CVL, and the spatial distribution of human and canine VL cases was compared using univariate and bivariate K-functions. Results: Human cases conglomerated in three neighborhoods. Spatial clusters were detected for CVL in 1998, 2000, and 2001, but not in 1999, when greater spatial dispersion occurred. The screening and culling intervention reduced the number of human VL cases and decreased the incidence of CVL, mainly in neighborhoods with a high CMI. Conclusions: The systematic euthanasia of seropositive dogs was shown to be an effective control action of the Program for Control of Visceral Leishmaniasis (PCLV) in Brazil. The fundamental role of domestic dogs in the epidemiological chain of VL was reaffirmed.

The public health surveillance of yachts and pleasure boats is relevant to avoid and prevent the spread of infectious diseases. With the entry into force of the International Health Regulations 2005, the Ship Sanitation Exemption Certificate (SSEC) become an important tool to prevent the risk of the international spread of disease through international maritime travel. The WHOs existing international guidelines mainly refer to large ships, so the aim of this work was to create a concise checklist applicable to the yachting world. In order to facilitate and standardise the inspection procedures on board yachts, a summary checklist was therefore drawn up. A summary of mainly non compliance founded in the 2021 is also provided.

Abstract Background Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. Methods Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. Results We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A—BoNT/A—had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score

Abstract The dynamic contrast-enhanced MR imaging plays a crucial role in evaluating the effectiveness of neoadjuvant chemotherapy (NAC) even since its early stage through the prediction of the final pathological complete response (pCR). In this study, we proposed a transfer learning approach to predict if a patient achieved pCR (pCR) or did not (non-pCR) by exploiting, separately or in combination, pre-treatment and early-treatment exams from I-SPY1 TRIAL public database. First, low-level features, i.e., related to local structure of the image, were automatically extracted by a pre-trained convolutional neural network (CNN) overcoming manual feature extraction. Next, an optimal set of most stable features was detected and then used to design an SVM classifier. A first subset of patients, called fine-tuning dataset (30 pCR; 78 non-pCR), was used to perform the optimal choice of features. A second subset not involved in the feature selection process was employed as an independent test (7 pCR; 19 non-pCR) to validate the model. By combining the optimal features extracted from both pre-treatment and early-treatment exams with some clinical features, i.e., ER, PgR, HER2 and molecular subtype, an accuracy of 91.4% and 92.3%, and an AUC value of 0.93 and 0.90, were returned on the fine-tuning dataset and the independent test, respectively. Overall, the low-level CNN features have an important role in the early evaluation of the NAC efficacy by predicting pCR. The proposed model represents a first effort towards the development of a clinical support tool for an early prediction of pCR to NAC.

Abstract Postzygotic mosaicism (PZM) in NIPBL is a strong source of causality for Cornelia de Lange syndrome (CdLS) that can have major clinical implications. Here, we further delineate the role of somatic mosaicism in CdLS by describing a series of 11 unreported patients with mosaic disease-causing variants in NIPBL and performing a retrospective cohort study from a Spanish CdLS diagnostic center. By reviewing the literature and combining our findings with previously published data, we demonstrate a negative selection against somatic deleterious NIPBL variants in blood. Furthermore, the analysis of all reported cases indicates an unusual high prevalence of mosaicism in CdLS, occurring in 13.1% of patients with a positive molecular diagnosis. It is worth noting that most of the affected individuals with mosaicism have a clinical phenotype at least as severe as those with constitutive pathogenic variants. However, the type of genetic change does not vary between germline and somatic events and, even in the presence of mosaicism, missense substitutions are located preferentially within the HEAT repeat domain of NIPBL. In conclusion, the high prevalence of mosaicism in CdLS as well as the disparity in tissue distribution provide a novel orientation for the clinical management and genetic counselling of families.

Legionella is a public health concern on passenger ships and the the need to implement a Legionellosis prevention plan is even more important in on-board hospitals that are frequented by higher risk people who are more susceptible to infection. In this paper we proposed a prevention plan specific for shipboard medical facilities derived by the Italian National guidelines for Legionellosis prevention. We presented also data of efficacy and performance specifications (field evaluation), on a Legionella point-of-use filter. The point-of-use filters when they are used in synergy with the others prevention methods can play an important role, cost–benefits ratio positive, to minimize the risk of growth and spread of Legionella and other waterborne pathogens on passenger ships in case of specific conditions.

The ribosomal protein S6 kinase 1 (S6K1) is a relevant effector downstream of the mammalian target of rapamycin complex 1 (mTORC1), best known for its role in the control of lipid homeostasis. Consistent with this, mice lacking the S6k1 gene have a defect in their ability to induce the commitment of fat precursor cells to the adipogenic lineage, which contributes to a significant reduction of fat mass. Here, we assess the therapeutic blockage of S6K1 in diet-induced obese mice challenged with LY2584702 tosylate, a specific oral S6K1 inhibitor initially developed for the treatment of solid tumors. We show that diminished S6K1 activity hampers fat mass expansion and ameliorates dyslipidemia and hepatic steatosis, while modifying transcriptome-wide gene expression programs relevant for adipose and liver function. Accordingly, decreased mTORC1 signaling in fat (but increased in the liver) segregated with defective epithelial-mesenchymal transition and the impaired expression of Cd36 (coding for a fatty acid translocase) and Lgals1 (Galectin 1) in both tissues. All these factors combined align with reduced adipocyte size and improved lipidomic signatures in the liver, while hepatic steatosis and hypertriglyceridemia were improved in treatments lasting either 3 months or 6 weeks.