Salmonellosis in Children at a Portuguese Hospital: A Retrospective Study.

INTRODUCTION: Salmonellosis represents a considerable health, social and economic burden in both high- and low-income countries. Recently, in Portugal, most cases of Salmonella infections have been reported in children under 15 years of age. The main aim of this study was to characterize, from an epidemiological, microbiological, and clinical perspective, cases of Salmonella isolation among children. MATERIAL AND METHODS: The authors performed a descriptive study using retrospective analysis of cases of salmonellosis, in pediatric age, at a Portuguese Level II Hospital, between January 2015 and July 2020. RESULTS: The population included a total of 63 children, of which 81% were Portuguese. Ethnicity was identified in 13 children, most of whom were African. The median age at diagnosis was four years old (3.5 - 9 years old). Despite the small number of cases per year in our study (11), one-third were severe enough to require hospitalization. Overall, 13% of patients were treated with antibiotics. In 63% of the isolates, serotype was identified: Salmonella Enteriditis (38%), Salmonella Typhimurium (22%), and Salmonella Typhi (3%). Antibiotic resistance rates were 19% for ampicillin and 6.4% for amoxicillinclavulanic acid and cotrimoxazole. No resistance to third-generation cephalosporins was found. CONCLUSION: Given the obtained results, we intend to improve knowledge on salmonellosis in Portugal and, consequently improve prevention strategies, treatment and its notification. Although the incidence of salmonellosis has been decreasing in recent years it is the second most frequent gastrointestinal infection in the European Union, contributing to significant rates of hospitalizations and use of antibiotics in Portugal.

Characterization of Jasmonoyl-Isoleucine (JA-Ile) Hormonal Catabolic Pathways in Rice upon Wounding and Salt Stress.

BACKGROUND: Jasmonate (JA) signaling and functions have been established in rice development and response to a range of biotic or abiotic stress conditions. However, information on the molecular actors and mechanisms underlying turnover of the bioactive jasmonoyl-isoleucine (JA-Ile) is very limited in this plant species. RESULTS: Here we explored two gene families in rice in which some members were described previously in Arabidopsis to encode enzymes metabolizing JA-Ile hormone, namely cytochrome P450 of the CYP94 subfamily (CYP94, 20 members) and amidohydrolases (AH, 9 members). The CYP94D subclade, of unknown function, was most represented in the rice genome with about 10 genes. We used phylogeny and gene expression analysis to narrow the study to candidate members that could mediate JA-Ile catabolism upon leaf wounding used as mimic of insect chewing or seedling exposure to salt, two stresses triggering jasmonate metabolism and signaling. Both treatments induced specific transcriptional changes, along with accumulation of JA-Ile and a complex array of oxidized jasmonate catabolites, with some of these responses being abolished in the JASMONATE RESISTANT 1 (jar1) mutant. However, upon response to salt, a lower dependence on JAR1 was evidenced. Dynamics of CYP94B5, CYP94C2, CYP94C4 and AH7 transcripts matched best the accumulation of JA-Ile catabolites. To gain direct insight into JA-Ile metabolizing activities, recombinant expression of some selected genes was undertaken in yeast and bacteria. CYP94B5 was demonstrated to catalyze C12-hydroxylation of JA-Ile, whereas similarly to its Arabidopsis bi-functional homolog IAR3, AH8 performed cleavage of JA-Ile and auxin-alanine conjugates. CONCLUSIONS: Our data shed light on two rice gene families encoding enzymes related to hormone homeostasis. Expression data along with JA profiling and functional analysis identifies likely actors of JA-Ile catabolism in rice seedlings. This knowledge will now enable to better understand the metabolic fate of JA-Ile and engineer optimized JA signaling under stress conditions.

Camp Raising Spirits: An Oncology Nursing Society Chapter Leadership Success Story
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Oncology Nursing Society (ONS) members share a unique passion for the people they serve and frequently commit to projects that make a difference. Camp Raising Spirits, a weekend retreat for adults with cancer, has made a difference in southwestern Pennsylvania for hundreds of people with cancer and their caregivers for 24 consecutive years. This article will describe how an ONS chapter capitalized on the leadership attributes of partnership, creativity, and commitment to sustain an important community service program. 
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Simple and high yield access to octafunctional azido, amine and urea group bearing cubic spherosilicates.

Spherosilicates and polyhedral oligomeric silsesquioxanes represent unique well-defined rigid building blocks for molecular and hybrid materials. Drawbacks in their synthesis are often low yields and the restricted presence of functional groups either based on incomplete transformation of all corners or the reactivity of the functional groups. Particularly amine-functionalization reveals some synthetic challenges. In this study we report the synthesis of a new class of octafunctionalized hydrogen bond forming spherosilicates via a facile route based on octabromo alkyl functionalized cubic spherosilicates. Four different alkyl chain lengths, namely C4, C5, C6 and C11, were realized starting from ω-alkenylbromides via hydrosilylation of Q8M8H. Using sodium azide in a mixture of acetonitrile : DMF = 10 : 1, the octaazide was obtained quantitatively and could be rapidly transformed in an octaamine cube via catalytic hydrogenation over Pd/C in absolute ethanol. The following reaction to hydrogen bond forming spherosilicates was performed in situ by adding propyl isocyanate. All transformations proceed quantitatively at the eight corners of the cube, which was evidenced by NMR spectroscopy and ESI-MS measurements. The Q8-target compound can be separated after each reaction step over simple chemical workup while no cage rearrangement was observed. The structures were confirmed using 1H, 13C, 29Si-NMR, FT-IR, elemental analysis and ESI-MS. The method opens a high yield route (overall isolated yield 83-88%) for structural building blocks in hybrid materials.

Tetraspanin CD63 acts as a pro-metastatic factor via ß-catenin stabilization.

The tetraspanin CD63 is implicated in pro-metastatic signaling pathways but, so far, it is unclear, how CD63 levels affect the tumor cell phenotype. Here, we investigated the effect of CD63 modulation in different metastatic tumor cell lines. In vitro, knock down of CD63 induced a more epithelial-like phenotype concomitant with increased E-cadherin expression, downregulation of its repressors Slug and Zeb1, and decreased N-cadherin. In addition, ß-catenin protein was markedly reduced, negatively affecting expression of the target genes MMP-2 and PAI-1. ß-catenin inhibitors mimicked the epithelial phenotype induced by CD63 knock down. Inhibition of ß-catenin upstream regulators PI3K/AKT or GSK3ß could rescue the mesenchymal phenotype underlining the importance of the ß-catenin pathway in CD63-regulated cell plasticity. CD63 knock down-induced phenotypical changes correlated with a decrease of experimental metastasis whereas CD63 overexpression enhanced the tumor cell-intrinsic metastatic potential. Taken together, our data show that CD63 is a crucial player in the regulation of the tumor cell-intrinsic metastatic potential by affecting cell plasticity.

Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study.

Transdermal methimazole is suggested as an alternative to oral therapy for hyperthyroid cats that are difficult to pill. However, no information on long-term management with this treatment is available. Our objective was therefore to retrospectively evaluate the efficacy and safety of long-term transdermal methimazole treatment in hyperthyroid cats. Sixty cats with newly diagnosed hyperthyroidism and available long-term follow-up information were included. Methimazole was formulated in a pluronic lecithin organogel-based vehicle and was applied to the pinna of the inner ear. Cats were re-evaluated at regular intervals. Median (range) follow-up was 22.6 months (3.6-88.4 months). Clinical improvement was observed in all cats and side effects were rare (mild transient gastrointestinal signs: n = 3; erythema of the pinna: n = 2, necessitating a switch to oral medication). Despite a significant decrease, with median T4 concentrations within the reference interval during the follow-up period, several cats repeatedly had T4 concentrations in the thyrotoxic and hypothyroid range. Maximal and minimal daily doses during the follow-up period were 15.0 and 1.0 mg, respectively; they were significantly higher than the starting dose after 24-36 months of therapy. Although the majority of owners were highly satisfied with the treatment, several admitted not treating their cat regularly. Transdermal methimazole is a safe option for the long-term management of feline hyperthyroidism. However, it seems difficult to keep the T4 concentrations constantly within the reference interval. Higher doses can be expected after prolonged treatment and, despite the convenience of transdermal application, owner compliance should be assessed regularly.

Determination of perfluorinated alkyl acid concentrations in biological standard reference materials.

Standard reference materials (SRMs) are homogeneous, well-characterized materials used to validate measurements and improve the quality of analytical data. The National Institute of Standards and Technology (NIST) has a wide range of SRMs that have mass fraction values assigned for legacy pollutants. These SRMs can also serve as test materials for method development, method validation, and measurement for contaminants of emerging concern. Because inter-laboratory comparison studies have revealed substantial variability of measurements of perfluoroalkyl acids (PFAAs), future analytical measurements will benefit from determination of consensus values for PFAAs in SRMs to provide a means to demonstrate method-specific performance. To that end, NIST, in collaboration with other groups, has been measuring concentrations of PFAAs in a variety of SRMs. Here we report levels of PFAAs and perfluorooctane sulfonamide (PFOSA) determined in four biological SRMs: fish tissue (SRM 1946 Lake Superior Fish Tissue, SRM 1947 Lake Michigan Fish Tissue), bovine liver (SRM 1577c), and mussel tissue (SRM 2974a). We also report concentrations for three in-house quality-control materials: beluga whale liver, pygmy sperm whale liver, and white-sided dolphin liver. Measurements in SRMs show an array of PFAAs, with perfluorooctane sulfonate (PFOS) being the most frequently detected. Reference and information values are reported for PFAAs measured in these biological SRMs.

Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography-mass spectrometry.

Peptide quantification by liquid chromatography-mass spectrometry (LC-MS) combines the high resolving power of reversed-phase (RP) chromatography with the excellent selectivity and sensitivity of mass spectrometric detection. On the basis of comprehensive practical experience in the analysis of small molecules, pharmaceutical research is developing technologies for analysis of a growing number of peptidic drug candidates. This article is a detailed review of procedures based on LC-MS techniques for quantitative determination of peptides. With the focus on pharmaceutical applications several technologies for sample preparation, various aspects of peptide chromatography, important characteristics of ESI-MS, selectivity of MS-detection modes, the large variability of internal standards, and modern instrumentation are discussed. The demand for reliable, robust, sensitive, and accurate methods is discussed using numerous examples from the literature, complemented by experiments and results from our laboratory.

No hypofrontality, but absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia.

Hypofrontality and decreased lateralization have been two major, albeit controversial, results from functional neuroimaging studies of schizophrenia. We used fMRI to study cortical activation during a verbal and spatial working memory (WM) task (2-back) in 15 inpatients acutely ill with schizophrenia and 15 matched control subjects. We hypothesized (i) hypofrontality in patients in both tasks and (ii) decreased lateralization of prefrontal activation in patients under the assumption that, in controls, left prefrontal cortex (PFC) is engaged preferentially in the verbal task (verbal domain dominance) and the right prefrontal cortex is engaged preferentially in the spatial task (spatial domain dominance). Our results showed no significant differences in frontal activation between controls and patients, i.e. no hypofrontality in patients, even at a very liberal threshold (p<0.01). This may be explained by the fact that nearly all patients studied received atypical neuroleptics. Nonetheless, we found evidence for more subtle, domain-related prefrontal dysfunction. Whereas controls showed verbal WM domain dominance in left inferior frontal cortex and spatial WM domain dominance in right prefrontal cortex, these domain dominance effects were absent in the patient group, i.e. there were no lateralization effects. Finally, only patients showed an inverse correlation between performance and right prefrontal activation in verbal WM. We conclude that the finding of hypofrontality may depend on the medication of the patients and that there is prefrontal dysfunction even in the absence of hypofrontality.