Local Antimicrobial Resistance Trends in Pediatric Urinary Tract Infection: The Importance of Local Surveillance of a Global Problem.

Introduction Urinary tract infections (UTIs) are one of the most common pediatric bacterial infections and consequently a major reason for antibiotic treatment. Despite being a global problem, antimicrobial resistance is often geographically heterogeneous. Thus, it is fundamental to know local epidemiology and practice frequent surveillance of each hospital's antibiograms. The aims of this study are to determine the local antimicrobial resistance profile in pediatric UTIs, to understand its evolution over 14 years, and finally, to infer if the currently instituted antibiotic empirical therapy remains effective. Materials and methods A retrospective observational study was performed through the analysis of urine cultures and respective antibiograms of children diagnosed with UTI from 2017 to 2019 in Centro Hospitalar Universitário do Algarve (Faro's unit, Portugal), followed by a comparison of the obtained data with the results of a similar study performed between 2003 and 2005. Results A total of 784 urine cultures were selected. Escherichia coli was the most frequent microorganism (n = 561; 71.56%), followed by Proteus mirabilis (n = 117; 14.92%) and Klebsiella pneumoniae (n = 40; 5.10%). The most commonly prescribed antibiotic was cefuroxime axetil (66.28%). Escherichia coli had an increase in resistance to amoxicillin-clavulanate of 6.16% to 34.76% and cefuroxime axetil of 0.73% to 4.46%. Proteus mirabilis had an increase in resistance to amoxicillin-clavulanate of 1.64% to 11.11%. Klebsiella pneumoniae had an increase in resistance to cefuroxime axetil (0%-27.50%) and nitrofurantoin (0%-47.50%). The three microorganisms showed a decrease in trimethoprim-sulfamethoxazole resistance profiles, as well as low resistance profiles to fosfomycin. In fifty cases in which antibiotic empirical therapy was instituted, the isolated microorganism revealed in vitro resistance; 37 of these cases had a good evolution, maintaining the antibiotic empirical therapy. Discussion Local surveillance of antimicrobial resistance allows monitoring of the resistance trends and adequacy of empirical antibiotic therapy. This study's local resistance profile was distinct from other regions of the country and the world. Continuous local surveillance also potentiates the dissemination of the results to the concerned healthcare providers and the initiation of timely responsive measures, containing the increase in antimicrobial resistance. As Escherichia coli was the commonest isolated microorganism, its antimicrobial profile should dictate antibiotic empirical therapy. This study supports that in vitro is not equivalent to in vivo resistance. Conclusion There was a significant increase in antimicrobial resistance profiles, especially to amoxicillin-clavulanate. Cefuroxime axetil remains the recommended antibiotic for empirical therapy in this hospital, although fosfomycin should be considered as an alternative in non-complicated cystitis in adolescent females. This study reinforces the importance of continuous local resistance surveillance as a preventive measure against the global increase in antimicrobial resistance.

The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes.

Epigenetic regulators are frequently mutated in hematological malignancies including acute myeloid leukemia (AML). Thus, the identification and characterization of novel epigenetic drivers affecting AML biology holds potential to improve our basic understanding of AML and to uncover novel options for therapeutic intervention. To identify novel tumor suppressive epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML. This identified the Histone 3 Lysine 4 (H3K4) demethylase KDM5C as a tumor suppressor, and we show that reduced Kdm5c/KDM5C expression results in accelerated growth both in human and murine AML cell lines, as well as in vivo in Cebpa mutant and inv(16) AML mouse models. Mechanistically, we show that KDM5C act as a transcriptional repressor through its demethylase activity at promoters. Specifically, KDM5C knockdown results in globally increased H3K4me3 levels associated with up-regulation of bivalently marked immature genes. This is accompanied by a de-differentiation phenotype that could be reversed by modulating levels of several direct and indirect downstream mediators. Finally, the association of KDM5C levels with long-term disease-free survival of female AML patients emphasizes the clinical relevance of our findings and identifies KDM5C as a novel female-biased tumor suppressor in AML.

Kiwi Plant Canker Diagnosis Using Hyperspectral Signal Processing and Machine Learning: Detecting Symptoms Caused by Pseudomonas syringae pv. actinidiae.

Pseudomonas syringae pv. actinidiae (Psa) has been responsible for numerous epidemics of bacterial canker of kiwi (BCK), resulting in high losses in kiwi production worldwide. Current diagnostic approaches for this disease usually depend on visible signs of the infection (disease symptoms) to be present. Since these symptoms frequently manifest themselves in the middle to late stages of the infection process, the effectiveness of phytosanitary measures can be compromised. Hyperspectral spectroscopy has the potential to be an effective, non-invasive, rapid, cost-effective, high-throughput approach for improving BCK diagnostics. This study aimed to investigate the potential of hyperspectral UV-VIS reflectance for in-situ, non-destructive discrimination of bacterial canker on kiwi leaves. Spectral reflectance (325-1075 nm) of twenty plants were obtained with a handheld spectroradiometer in two commercial kiwi orchards located in Portugal, for 15 weeks, totaling 504 spectral measurements. Several modeling approaches based on continuous hyperspectral data or specific wavelengths, chosen by different feature selection algorithms, were tested to discriminate BCK on leaves. Spectral separability of asymptomatic and symptomatic leaves was observed in all multi-variate and machine learning models, including the FDA, GLM, PLS, and SVM methods. The combination of a stepwise forward variable selection approach using a support vector machine algorithm with a radial kernel and class weights was selected as the final model. Its overall accuracy was 85%, with a 0.70 kappa score and 0.84 F-measure. These results were coherent with leaves classified as asymptomatic or symptomatic by visual inspection. Overall, the findings herein reported support the implementation of spectral point measurements acquired in situ for crop disease diagnosis.

Stroke and refractory hypoxaemia: complications of pulmonary embolism.

Acute pulmonary embolism is one of the main causes of cardiovascular mortality. Treatment should be guided according to mortality risk stratification, but an individualised and multidisciplinary approach is often required. Concomitant persistent hypoxaemia can be present in cases of intracardiac shunt. In this report, we describe a 46-year-old woman with a history of surgery, presenting with pulmonary embolism with refractory hypoxaemia and simultaneous ischaemic stroke. Fibrinolysis was successfully performed, and the patient made a full recovery. Additional investigations identified a patent foramen ovale, which was later closed. She had no recurrent thrombotic events.

Myasthenia gravis and prostatic neoplasia: a rare association.

An 88-year-old male patient presented with left ptosis, diplopia, muscle weakness of the lower limbs, dysphagia for solids, dysphonia and constipation. On investigation, he was found to have myasthenia gravis (MG). Further evaluation for the possible cause of MG, with CT scan, revealed that the patient had concomitant prostatic cancer. The patient was given steroids and pyridostigmine, with consequent resolution of his neurological symptoms. This is a rare case of MG associated with prostatic cancer.

Effects of ultrasonic irradiation on crystallization kinetics, morphological and structural properties of zeolite FAU.

In this work, NaX zeolite was synthesized and the effect of ultrasound irradiation on reaction kinetics, morphological and structural properties was investigated. Ultrasound was applied, by using a plate transducer (91.8 kHz), for the first time during the crystallization of zeolite NaX, at high temperature, varying the irradiation moment and its duration. Furthermore, ultrasound was applied after the crystallization by a horn-type transducer (20-24 kHz) at low temperature. The effects of irradiated volume (100-300 mL), sonication time (2-10 min) and ultrasound power (10-200 W) were studied with a power intensity up to 100 W/cm2. It was found that the application of ultrasound during the first hour of crystallization resulted in 20% reduction of reaction time compared to a standard crystallization. Ultrasound can also reduce the agglomeration degree of the final powder by combining high power and long sonication time. After 5 min sonication time at 0.3 W/mL, the tapped density of the powder was increased by 10%, from 0.37 to 0.41 g/mL. Finally, by scanning electron microscopy (SEM) it was demonstrated that ultrasound can disrupt the agglomerates without affecting the morphology of individual crystals.

Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit.

Anorexigenic pro-opiomelanocortin (Pomc)/alpha-melanocyte stimulating hormone (αMSH) neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst)-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH) expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful.

Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance.

Low-grade inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Interleukin-6 (IL-6) is a crucial regulator of T cells and is increased in obesity. Here we report that classical IL-6 signalling in T cells promotes inflammation and insulin resistance during the first 8 weeks on a high-fat diet (HFD), but becomes dispensable at later stages (after 16 weeks). Mice with T cell-specific deficiency of IL-6 receptor-α (IL-6RαT-KO) exposed to a HFD display improved glucose tolerance, insulin sensitivity and inflammation in liver and EWAT after 8 weeks. However, after 16 weeks, insulin resistance in IL-6RαT-KO epididymal white adipose tissue (EWAT) is comparable to that of controls, whereas the inflammatory profile is significantly worse. This coincided with a shift from classical T cell IL-6 signalling at 8 weeks, to enhanced IL-6 trans-signalling at 16 weeks. Collectively, our studies reveal that IL-6 action in T cells through classical IL-6 signalling promotes inflammation and insulin resistance early during obesity development, which can be compensated for by enhanced IL-6 trans-signalling at later stages.

Stress, burnout e avaliação cognitiva: estudo na classe de enfermagem / Stress, burnout and cognitive appraisal: a study with nurses / Estrés, agotamiento y evaluación cognitiva: un estudio dos profesionales de enfermería

Este estudo analisa o stress laboral em enfermeiros, observando igualmente a importância dos processos de avaliação cognitiva no ajustamento aos contextos de trabalho. Foram aplicados, em um único momento, a 153 profissionais da classe de enfermagem instrumentos de avaliação do stress ocupacional, da avaliação cognitiva primária e secundária, do burnout e da sintomatologia depressiva. Os níveis de stress, de burnout e de sintomatologia depressiva confirmaram que essa profissão é exigente do ponto de vista emocional e psicológico. Os processos de avaliação cognitiva foram determinantes na explicação da experiência de stress ocupacional, burnout e sintomatologia depressiva. O stress ocupacional e a avaliação cognitiva foram variáveis importantes na predição do burnout. Os resultados deste estudo evidenciaram o papel central da avaliação cognitiva na adaptação humana aos contextos de trabalho bem como a utilidade do modelo transacional no estudo do stress laboral.

This study analyzes the occupational stress in nurses, observing also the importance of cognitive appraisal in the adjustment to work contexts. In a single moment, evaluation protocols that included instruments of occupational stress, primary and secondary cognitive appraisals, burnout, and depressive symptomatology were applied to 153 nurses. Levels of occupational stress, burnout, and depressive symptomatology have confirmed that this activity is very demanding, both on emotional and psychological levels. The processes of cognitive appraisal were determining factors in the comprehension of occupational stress, burnout, and depressive symptomatology. Occupational stress and cognitive appraisals dimensions were predictors of the burnout experience. The results of this study pointed out the central role of the cognitive appraisals in the human adaptation to the work contexts and the usefulness of the transactional model in the study of occupational stress.

Este estudio analiza el estrés laboral en profesionales de enfermería, observando también la importancia de la evaluacion cognitiva en la adaptación al trabajo. Mediante una metodología transversal, se aplicó un protocolo de evaluación a 153 profesionales de enfermería con instrumentos de estrés ocupacional, evaluación cognitivas primaria y secundaria, agotamiento y sintomatología depresiva. Los niveles de estrés laboral, agotamiento y sintomatología depresiva confirmaron que esta actividad es muy exigente a nivel psicológico y emocional. Los procesos de evaluación cognitiva fuerwon cruciales para explicar la experiencia de estrés laboral, de agotamiento y de sintomatología depresiva. El estrés laboral y la evaluación cognitiva fueron variables importantes en la predicción de agotamiento. Los resultados de este estudio demonstraron el papel central de la evaluación cognitiva en la adaptación humana al trabajo y la utilidad del modelo transaccional en el estudio del estrés laboral.