The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI.

COVID-19 is generally mild in children, 1 and post-acute inflammatory conditions that are temporally associated with the virus are rare, but potentially severe. However, some children and adults experience persistent symptoms after COVID-19. 2 Long COVID has not been precisely defined, but one study reported symptoms approximately 60 days after the primary diagnosis. 3 Although adult long COVID is increasingly being studied, the magnitude of persistent symptoms in children remains unclear. This Swedish study assessed the extent, and type, of persistent symptoms in children aged 0-18 years who were admitted to one of the two paediatric hospitals in the Stockholm Region from 13 March to 31 August 2020 due to COVID-19. The inclusion criteria were the presence of a nasopharyngeal sample RT-PCR positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Children that tested positive, but were hospitalised for other reasons, were not included. Information on any persisting health issues following BRIEF REPORT

The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated by Escherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring. Interstitial fibrosis is the final common end-point of progressive renal diseases. Despite its clinical significance, the mechanisms of scar formation in the kidney are still not fully understood. Generally, it is thought that the renal fibrogenesis is induced by the release of chemokines and growth factors by a number of resident cells. Their concentration gradient results in an influx of leukocytes and an increase in the number of interstitial fibroblasts. The induction phase is followed by an increased matrix production and reduced matrix degradation, which add up to a deposition of extracellular matrix (ECM) components (1). However, ECM component deposition does not seem to be the only mechanism in the pathogenesis of scarring. After direct inoculation of Escherichia coli into the kidneys of rats, contraction and collapse of the tubulointerstitial parenchyma had a greater influence than new collagen production on final fibrosis (2). In line with that, we have previously shown that mouse kidneys after experimental acute pyelonephritis were smaller compared with those from uninfected animals (3). Likewise, it seems that the end-stage kidney is rather shrunken, not enlarged or full of collagen (4).The current hypothesis suggests that the normal remodeling and healing is a result of the balance between ECM protein synthesis and degradation (5). Out of a number of matrixdegrading enzymes, gelatinases, matrix metallopro...

According to the United Nations Educational, Science and Cultural Organization, 194 countries had implemented country-wide school closures by April 1, 2020, in an effort to combat the COVID-19 pandemic. It is estimated that those closures affected 91.3% of students across the globe. However, Sweden adopted a different approach to the strict lockdowns imposed elsewhere and day-care centres and schools for children up to 15 years of age remained open. The

BackgroundAn understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses.MethodsWe performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020.ResultsA total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses.ConclusionsSARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

SUMMARYThe aim of the present study was to investigate the effects of IL-1 b and Escherichia coli on the expression and secretion of MIP-2, the mouse equivalent to human IL-8, MCP-1 and RANTES in the kidneys of mice with acute pyelonephritis. Female Bki NMRI, as well as IL-1 b deficient mice and their wild-type littermates, were transurethrally infected with either E. coli CFT 073 or injected with NaCl 0·9% (w/v) and thereafter obstructed for 6 h. The Bki NMRI mice were killed at 0, 24, 48 h and 6 days and the IL-1 b -deficient mice at 48 h. Chemokine mRNA and protein levels peaked at 24 h for the tested chemokines with the mRNA expression localized in the tubular epithelial cells and for MIP-2 also in neutrophils. Obstruction per se , also induced a chemokine expression similar to E. coli infection although at a lower level. Interestingly, MIP-2 levels were higher in the IL-1 b deficient mice as compared with the wild-type littermates. Likewise, the inflammatory changes were more frequent and, when present, more widespread in the IL-1 b -deficient mice than in the wild-type mice. Stimulation of a human renal tubular epithelial cell line (HREC), A498 and of primary human mesangial cells (HMC) with the same bacterial antigen depicted gene expression of the same chemokines. A rapid release of IL-8 and MCP-1 was observed from both cell types. RANTES response was delayed both in the HREC and the HMC. We conclude that acute E. coli pyelonephritis induces a MIP-2/IL-8, MCP-1 and RANTES expression and secretion localized primarily to the epithelial cells and that this production is confirmed after in vitro stimulation with the same bacterial antigen of human epithelial and mesangial cells. Blockade of induction of chemokine response may thus be an attractive target for possible therapeutic intervention.

Tight junction proteins are pivotal to prevent bacterial invasion of the epithelial barrier. We here report that supplementation with vitamin D can strengthen the urinary bladder lining. Vitamin D deficient and sufficient mice were infected with Escherichia coli (E. coli) transurethrally to cause urinary tract infection. In addition, bladder biopsies were obtained from postmenopausal women before and after a 3-month period of supplementation with 25-hydroxyvitamin D3 (25D3) and ex vivo infected with E. coli. In biopsies, obtained before E. coli infection, vitamin D had no impact on tight junction proteins. However, during E. coli infection, vitamin D induced occludin and claudin-14 in mature superficial umbrella cells of the urinary bladder, as demonstrated by immunohistochemistry. Increased cell-cell adhesion consolidating the epithelial integrity is thereby promoted. We here describe a novel role of vitamin D in the urinary tract supporting vitamin D supplementation to restore the bladder epithelial integrity.

Our data demonstrate that infectious complications contribute significantly to morbidity in children with cancer aged 7-16 years. At the time of this survey, antibiotic prescription patterns varied and cephalosporins and carbapenems were mostly used. With increasing antibiotic resistance, a more stringent antibiotic stewardship with less use of cephalosporins and carbapenems should be encouraged for children with cancer. Data on prescription patterns should be incorporated as a quality measurement in pediatric cancer care.