Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Economic burden of skin and skin structure infections due to Gram-positive bacteria in patients on hospital at home-based outpatient parenteral antibiotic therapy (OPAT) / Carga económica de la infección de piel y partes blandas por microorganismos grampositivos en pacientes en unidades de hospitalización a domicilio con tratamiento antimicrobiano domiciliario endovenoso (TADE)

Objective: To describe and quantify resource use and direct health costs associated with skin and skin structure infections (SSSIs) caused by Gram-positive bacteria in adults receiving outpatient parenteral antimicrobial therapy (OPAT), administered by Hospital at Home units (HaH) in Spain. Material and method: Observational, multicenter, retrospective study. We included patients of both sexes included in the HaH-based OPAT Registry during 2011 to 2017 who were hospitalized due to SSSIs caused by Gram-positive bacteria. Resource use included home visits (nurses and physician), emergency room visits, conventional hospitalization stay, HaH stay and antibiotic treatment. Costs were quantified by multiplying the natural units of the resources by the corresponding unit cost. All costs were updated to 2019 euros. Results: We included 194 episodes in 189 patients from 24 Spanish hospitals. The most frequent main diagnoses were cellulitis (26.8%) and surgical wound infection (24.2%), and 94% of episodes resulted in clinical improvement or cure after treatment. The median HaH stay was 13 days (interquartile range [IR]:8-22.7), and the conventional hospitalization stay was 5 days (IR: 1-10.7). The mean total cost attributable to the complete infectious process was €7,326 (95% confidence interval: €6,316-€8,416). Conclusions: Our results suggest that OPAT administered by HaH is a safe and efficient alternative for the management of these infections and could lead to lower costs compared with hospital admission. (AU)

Objetivo: Describir y cuantificar el uso de recursos y costes directos sanitarios asociados con las infecciones de piel y tejidos blandos (IPPB) causadas por microorganismos grampositivos en adultos que recibieron tratamiento antimicrobiano domiciliario endovenoso (TADE), administrado en unidades de hospitalización a domicilio (HaD) en España. Material y métodos: Estudio observacional, multicéntrico, retrospectivo. Se incluyeron pacientes adultos de ambos sexos, incluidos en el Registro TADE en el periodo 2011 a 2017y cuyo motivo de ingreso fue una IPPB causada por un microorganismo Grampositivo. El uso de recursos incluyó las visitas a domicilio (enfermería y médico), visitas a urgencias, estancia en hospitalización convencional, estancia en HaD y tratamiento antibiótico. Los costes se cuantificaron multiplicando las unidades naturales de los recursos por el coste unitario correspondiente. Todos los costes fueron actualizados a euros de 2019. Resultados: Se incluyeron 194 episodios (189 pacientes) procedentes de 24 centros españoles. Los diagnósticos principales más frecuentes fueron celulitis (26,8%) e infección por herida quirúrgica (24,2%). El 94% de los episodios resultaron en una mejoría o curación clínica al finalizar el tratamiento. La mediana de la estancia en HaD fue de 13 días (rango intercuartílico [RI]:8-22,7), con una estancia previa en hospitalización convencional de 5 días (RI: 1-10,7). El coste total promedio atribuible al proceso infecciosos completo fue de 7.326€ (intervalo de confianza del 95%: 6.316€-8.416€). Conclusiones: Este estudio sugiere que el TADE administrado en HaD es una alternativa segura y eficiente para el manejo de estas infecciones y podría conducir a menores costes en comparación con el ingreso hospitalario. (AU)

Orchard Management and Incorporation of Biochemical and Molecular Strategies for Improving Drought Tolerance in Fruit Tree Crops.

Water scarcity is one of the greatest concerns for agronomy worldwide. In recent years, many water resources have been depleted due to multiple factors, especially mismanagement. Water resource shortages lead to cropland expansion, which likely influences climate change and affects global agriculture, especially horticultural crops. Fruit yield is the final aim in commercial orchards; however, drought can slow tree growth and/or decrease fruit yield and quality. It is therefore necessary to find approaches to solve this problem. The main objective of this review is to discuss the most recent horticultural, biochemical, and molecular strategies adopted to improve the response of temperate fruit crops to water stress. We also address the viability of cultivating fruit trees in dry areas and provide precise protection methods for planting fruit trees in arid lands. We review the main factors involved in planting fruit trees in dry areas, including plant material selection, regulated deficit irrigation (DI) strategies, rainwater harvesting (RWH), and anti-water stress materials. We also provide a detailed analysis of the molecular strategies developed to combat drought, such as Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) through gene overexpression or gene silencing. Finally, we look at the molecular mechanisms associated with the contribution of the microbiome to improving plant responses to drought.

Oligometastatic Hormone-Sensitive Prostate Cancer. Why Radiotherapy?

Androgen deprivation therapy (ADT) has been considered for years the standard initial treatment for patients with metastatic prostate cancer (mPC). Recently published results support the use of taxanes, second-generation antiandrogens or radiotherapy to the primary tumor as part of the treatment in these patients, considering ADT alone as suboptimal. Metastasis-directed therapy (MDT) is used as part of the treatment for oligometastatic patients in different tumor types. In oligometastatic hormone-sensitive prostate cancer the role of MDT is being studied with promising results. In the present review we assess the available evidence for radiotherapy to the primary tumor in newly diagnosed mPC and for MDT in oligometastatic prostate cancer, as well as future directions in this clinical setting.

Monitoring Apricot (Prunus armeniaca L.) Ripening Progression through Candidate Gene Expression Analysis.

This study aimed at the monitoring of the apricot (Prunus armeniaca L.) ripening progression through the expression analysis of 25 genes related to fruit quality traits in nine cultivars with great differences in fruit color and ripening date. The level of pigment compounds, such as anthocyanins and carotenoids, is a key factor in food taste, and is responsible for the reddish blush color or orange skin and flesh color in apricot fruit, which are desirable quality traits in apricot breeding programs. The construction of multiple linear regression models to predict anthocyanins and carotenoids content from gene expression allows us to evaluate which genes have the strongest influence over fruit color, as these candidate genes are key during biosynthetic pathways or gene expression regulation, and are responsible for the final fruit phenotype. We propose the gene CHS as the main predictor for anthocyanins content, CCD4 and ZDS for carotenoids content, and LOX2 and MADS-box for the beginning and end of the ripening process in apricot fruit. All these genes could be applied as RNA markers to monitoring the ripening stage and estimate the anthocyanins and carotenoids content in apricot fruit during the ripening process.

sRNA Analysis Evidenced the Involvement of Different Plant Viruses in the Activation of RNA Silencing-Related Genes and the Defensive Response Against Plum pox virus of 'GF305' Peach Grafted with 'Garrigues' Almond.

Plum pox virus (PPV) causes sharka disease in Prunus trees. Peach (P. persica) trees are severely affected by PPV, and no definitive source of genetic resistance has been identified. However, previous results showed that PPV-resistant 'Garrigues' almond (P. dulcis) was able to transfer its resistance to 'GF305' peach through grafting, reducing symptoms and viral load in PPV-infected plants. A recent study tried to identify genes responsible for this effect by studying messenger RNA expression through RNA sequencing in peach and almond plants, before and after grafting and before and after PPV infection. In this work, we used the same peach and almond samples but focused the high-throughput analyses on small RNA (sRNA) expression. We studied massive sequencing data and found an interesting pattern of sRNA overexpression linked to antiviral defense genes that suggested activation of these genes followed by downregulation to basal levels. We also discovered that 'Garrigues' almond plants were infected by different plant viruses that were transferred to peach plants. The large amounts of viral sRNA found in grafted peaches indicated a strong RNA silencing antiviral response and led us to postulate that these plant viruses could be collaborating in the observed "Garrigues effect."

Educational trends post COVID-19 in engineering: Virtual laboratories.

The rapid advance of Information and Communication Technology (ICT) in recent times and the current pandemic caused by COVID-19 have profoundly transformed society and the economy in most of the world. The education sector has benefited from this ICT-driven revolution, which has provided and expanded multiple new tools and teaching methods that did not exist just a few decades ago. In light of this technological change, virtual laboratories (VLs) based on the use of virtual reality (VR) have emerged, which are increasingly used to facilitate the teaching-learning process in a wide range of training activities, both academic and professional types. The set of advantages offered by this type of VL, the main of which are listed in this article, has made its use increasingly common as support for engineering classes at universities. This paper presents a study involving 420 engineering students from Spanish and Portuguese universities and associated analyses on the assessment of different parameters in various VLs designed by the authors. The results obtained indicate that, in general, VR-based VLs are widely accepted and demanded by students, who likewise consider real laboratories (RLs) necessary in face-to-face teaching. In the current post-COVID-19 educational scenario, VLs and RLs will coexist within the new hybrid models that combine face-to-face and online teaching and learning.

Blood Particulate Analogue Fluids: A Review.

Microfluidics has proven to be an extraordinary working platform to mimic and study blood flow phenomena and the dynamics of components of the human microcirculatory system. However, the use of real blood increases the complexity to perform these kinds of in vitro blood experiments due to diverse problems such as coagulation, sample storage, and handling problems. For this reason, interest in the development of fluids with rheological properties similar to those of real blood has grown over the last years. The inclusion of microparticles in blood analogue fluids is essential to reproduce multiphase effects taking place in a microcirculatory system, such as the cell-free layer (CFL) and Fähraeus-Lindqvist effect. In this review, we summarize the progress made in the last twenty years. Size, shape, mechanical properties, and even biological functionalities of microparticles produced/used to mimic red blood cells (RBCs) are critically exposed and analyzed. The methods developed to fabricate these RBC templates are also shown. The dynamic flow/rheology of blood particulate analogue fluids proposed in the literature (with different particle concentrations, in most of the cases, relatively low) is shown and discussed in-depth. Although there have been many advances, the development of a reliable blood particulate analogue fluid, with around 45% by volume of microparticles, continues to be a big challenge.

Electrical Conductivity of a Stretching Viscoelastic Filament.

Long polymeric chains highly stretched and aligned with the flow confer a strong mechanical anisotropy on a viscoelastic solution. The electrically-driven transport of free ions under such conditions is far from being understood. In this paper, we determine experimentally whether the above-mentioned deviation from isotropy affects the electric charge transport across the liquid. To this end, we measure the electrical conductivity in the flow (stretching) direction of the cylindrical liquid filament formed in the elasto-capillary thinning that arises during the breakup of a viscoelastic liquid bridge. First, we examine the behavior of monodisperse solutions of polyethylene oxide (PEO) in a mixture of glycerine and water. For all the concentrations and molecular weights considered, the filament conductivity remains practically the same as the isotropic conductivity measured under hydrostatic conditions. However, we observe a decrease in the electric current at the end of elasto-capillary regime which may partially be attributed to the reduction of the liquid conductivity. Then, we measure the conductivity of bidisperse solutions of PEO with very different molecular weights. In this case, a significant decrease in conductivity is observed as the filament radius decreases. This constitutes the first experimental evidence of ion mobility reduction in stretching viscoelastic filaments, a relevant effect in applications such as electrospinning.

Gene Expression Analysis of Induced Plum pox virus (Sharka) Resistance in Peach (Prunus persica) by Almond (P. dulcis) Grafting.

No natural sources of resistance to Plum pox virus (PPV, sharka disease) have been identified in peach. However, previous studies have demonstrated that grafting a "Garrigues" almond scion onto "GF305" peach rootstock seedlings heavily infected with PPV can progressively reduce disease symptoms and virus accumulation. Furthermore, grafting a "Garrigues" scion onto the "GF305" rootstock has been shown to completely prevent virus infection. This study aims to analyse the rewiring of gene expression associated with this resistance to PPV transmitted by grafting through the phloem using RNA-Seq and RT-qPCR analysis. A total of 18 candidate genes were differentially expressed after grafting "Garrigues" almond onto healthy "GF305" peach. Among the up-regulated genes, a HEN1 homolog stands out, which, together with the differential expression of RDR- and DCL2-homologs, suggests that the RNA silencing machinery is activated by PPV infection and can contribute to the resistance induced by "Garrigues" almond. Glucan endo-1,3-beta D-glucosidase could be also relevant for the "Garrigues"-induced response, since its expression is much higher in "Garrigues" than in "GF305". We also discuss the potential relevance of the following in PPV infection and "Garrigues"-induced resistance: several pathogenesis-related proteins; no apical meristem proteins; the transcription initiation factor, TFIIB; the speckle-type POZ protein; in addition to a number of proteins involved in phytohormone signalling.

Las crisis, las oportunidades y la hospitalización a domicilio / The crises, the opportunities... and the hospital-based home care services

Todas las crisis, con independencia de su naturaleza e intensidad, ocasionan víctimas y secuelas. Cuando esas crisis se producen en el terreno de la salud, los afectados sufren enfermedades y, en casos extremos, la muerte. La pandemia por coronavirus es un claro ejemplo de cómo las crisis sanitarias representan una amenaza real para nuestra salud y para nuestras vidas.(AU)

The Conversion of Human Tissue-Like Inflammatory Monocytes Into Macrophages.

Classical circulating LyC6high murine monocytes differentiate progressively from inflammatory tissue monocytes to mature macrophages (Mϕ) after entry into gut mucosa. This protocol provides a two-step in vitro culture method that replicates the human monocyte maturation cascade. First, purified circulating CD14+ CD16- monocytes exposed to granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFNγ), and interleukin 23 (IL-23) differentiate into tissue-like inflammatory monocytes. Next, addition of transforming growth factor beta (TGFß) plus interleukin 10 (IL-10) promotes their maturation into tissue-like Mϕ. Methods to sort these cells after culture are also provided. The fine-tuning of this system might open therapeutic avenues for chronic inflammatory disorders. © 2021 Wiley Periodicals LLC Basic Protocol 1: Isolation of human monocytes from peripheral blood Basic Protocol 2: First step culture for generation of inflammatory monocyte-like cells Basic Protocol 3: Second step culture for differentiation of inflammatory monocyte-like cells into macrophages Alternate Protocol: Sorting and culturing of inflammatory monocyte-like cells.

Emotional stability is related to 2D:4D and social desirability in women: Possible implications on subjective well-being and psychopathology.

Emotional stability-Neuroticism is a complex construct influenced by genetics and environmental factors. Women tend to exhibit higher neuroticism scores than men, which may be associated with an increased risk of suffering from some common mental conditions. Some authors have pointed out the influence of sex hormones, since they induce sexual differentiation of the brain that can lead to sex-specific behaviors. 2D:4D digit ratio is commonly used as a marker of prenatal sex hormones. In this study we analyzed whether there was an association between 2D:4D and personality measured through the BFQ in a homogeneous sample of 101 young women college students. We found a positive association between 2D:4D and emotional stability, as well as with its subdimensions emotion control and impulse control. This association could be quadratic and nonlinear. However, no association was found with the other four dimensions. We also measured anxiety, depression and global life satisfaction, variables related to neuroticism. We observed that emotional stability is positively associated to social desirability and global life satisfaction, and negatively related to anxiety and depression. On the other hand, we did not find any association between 2D:4D and anxiety, depression, and global life satisfaction. These results can be linked to other aspects such as subjective well-being and psychopathological symptoms. This study may help to better understand how these constructs are related and could lead to future projects to elucidated how these variables influence personality.

Success of single-balloon enteroscope-assisted endoscopic retrograde colangiopancreatography in patients with a modified anatomy.

We would like to congratulate Drs. Espinel and Pinedo for their excellent results in single-ballon enteroscopy-assisted ERCP recently published in REED(1).We also want to share our experience. Between 2015 and 2021 we have performed 31 procedures in 26 patients. Half of the procedures (45.16%) were performed in patients with Roux-en-Y hepatic jejunostomy. Eight of these (22.80%) had prior primary bile duct surgery and six (19.35%) had prior Whipple surgery. The other half of the procedures (54.8%) presented native papilla: 10 (32.25%) subtotal gastrectomy and seven (22.58%) gastric bypass surgery.

Differential Changes in Inflammatory Mononuclear Phagocyte and T-Cell Profiles within Psoriatic Skin during Treatment with Guselkumab vs. Secukinumab.

Cellular sources of IL-23 and IL-17A driving skin inflammation in psoriasis remain unclear. Using high-dimensional unsupervised flow cytometry analysis, mononuclear phagocytes and T cells were examined in the same lesions of patients before and during guselkumab (IL-23p19 blocker) or secukinumab (IL-17A blocker) treatment. Among CD11c+HLA-DR+ mononuclear phagocytes, CD64brightCD163-CD14brightCD1c-CD1a‒ inflammatory monocyte‒like cells were the predominant IL-23-producing cells and, together with CD64-CD163-CD14-IL-23p19-TNF-α+ inflammatory dendritic cell‒like cells, were increased in lesional compared with those in nonlesional skin taken from the same patient. Within T cells, CD8+CD49a+ and/or CD103+ tissue-resident memory T cells, CD4+CD25+FoxP3+ regulatory T cells, and CD4+CD49a-CD103- T cells were increased. Moreover, CD4+CD49a-CD103- T cells and the relatively rare CD8+ memory T cells equally contributed to IL-17A production. Both treatments decreased the frequencies of inflammatory monocyte‒like, inflammatory dendritic cell‒like, and CD4+CD49a-CD103- T cells. In contrast, guselkumab reduced memory T cells while maintaining regulatory T cells and vice versa for secukinumab. Neither drug modified the frequencies of IL-17A+IL‒17F+/- CD4+ or CD8+ T cells. This study reveals the identity of the major IL-23+ mononuclear phagocyte and IL-17+ T-cell subsets in psoriatic skin lesions and paves the way for a better understanding of the mode of action of drugs targeting the IL-23/IL-17A pathway in psoriasis.

Gamete binning: chromosome-level and haplotype-resolved genome assembly enabled by high-throughput single-cell sequencing of gamete genomes.

Generating chromosome-level, haplotype-resolved assemblies of heterozygous genomes remains challenging. To address this, we developed gamete binning, a method based on single-cell sequencing of haploid gametes enabling separation of the whole-genome sequencing reads into haplotype-specific reads sets. After assembling the reads of each haplotype, the contigs are scaffolded to chromosome level using a genetic map derived from the gametes. We assemble the two genomes of a diploid apricot tree based on whole-genome sequencing of 445 individual pollen grains. The two haplotype assemblies (N50: 25.5 and 25.8 Mb) feature a haplotyping precision of greater than 99% and are accurately scaffolded to chromosome-level.