Molecular and cellular pediatrics最新文献

Background: Non-invasive cardiac imaging has a growing role in diagnosis, differential diagnosis, therapy planning, and follow-up in children and adolescents with congenital and acquired cardiac diseases. This review is based on a systematic analysis of international peer-reviewed articles and additionally presents own clinical experiences. It provides an overview of technical advances, emerging clinical applications, and the aspect of artificial intelligence.

Main body: The main imaging modalities are echocardiography, CT, and MRI. For echocardiography, strain imaging allows a novel non-invasive assessment of tissue integrity, 3D imaging rapid holistic overviews of anatomy. Fast cardiac CT imaging new techniques-especially for coronary assessment as the main clinical indication-have significantly improved spatial and temporal resolution in adjunct with a major reduction in ionizing dose. For cardiac MRI, assessment of tissue integrity even without contrast agent application by mapping sequences is a major technical breakthrough. Fetal cardiac MRI is an emerging technology, which allows structural and functional assessment of fetal hearts including even 4D flow analyses. Last but not least, artificial intelligence will play an important role for improvements of data acquisition and interpretation in the near future.

Conclusion: Non-invasive cardiac imaging plays an integral part in the workup of children with heart disease. In recent years, its main application congenital heart disease has been widened for acquired cardiac diseases.

Insulin is used to treat neonatal hyperglycaemia when blood glucose concentrations are consistently high, and to treat neonatal diabetes. Within this brief report, a review of the existing literature is conducted to determine if intravenous administration of insulin should be proceeded by priming of the intravenous system, adding of albumin, or non-priming to get a stable insulin dose. Within this literature search, we focused on experimental insulin adsorption data (in vitro studies).

Shigellosis is one of the acute bowel infections and remains a serious public health problem in resource-poor countries. The present study aimed to survey the distribution of extended-spectrum β-lactamase (ESBL)-producing Shigella strains isolated from patients with diarrhea in northwest Iran. In the present cross-sectional study, from January 2019 to December 2020, 1280 fecal samples were collected from children with diarrhea in Ardabil, Iran. Multiplex PCR assay was applied for the presence of ipaH, invC, wbgZ, rfpB, and rfc genes to detect Shigella spp., Shigella sonnei, Shigella dysenteriae, Shigella flexneri, and Shigella boydii, respectively. Phenotypic detection of ESBL-producing isolates was carried out using the Double Disc Test (DDT). The frequency of main ESBL encoding genes including bla_CTX-M, bla_SHV, and bla_TEM was detected using multiplex PCR. The genetic similarity of S. sonnei isolates was determined using ERIC PCR. A total of 49 Shigella isolates (3.8%; 49/1280) including 42 (85.7%) S. sonnei, 5 (10.2%) S. flexneri, and 2 (4%) S. dysenteriae were identified. S. boydii was not detected in any fecal samples. ESBLs were produced by 10.2% of Shigella spp. including 3 S. sonnei, 1 S. flexneri, and 1 S. dysenteriae. The ESBL encoding genes include bla_CTX-M and bla_TEM found in 65.3% and 61.2% of isolates, respectively. bla_SHV gene was not detected in any isolates. The ERIC-PCR profiles allowed the differentiation of 42 S. sonnei strains into 6 clusters. Our study revealed a high frequency of ESBL-encoding genes among Shigella spp. in northwest Iran. The high prevalence of S. sonnei harboring ESBL genes, in the present work, is the main challenge for dysentery treatment, and this concern justifies the need for effective and regular monitoring of antibiotic usage among patients.

Background: Subcutaneous fat necrosis of the newborn (SCFN) is a rare disease occurring in the first days of life. Characteristically, the infants show hard nodules in subcutaneous tissue, purple or erythematous in color and appear on the upper back, cheeks, buttocks and limbs. In most cases, SCFN is a self-limiting disease, as the nodules disappear in up to 6 months. A severe complication associated with SCFN is hypercalcaemia. Pathophysiological mechanisms causing SCFN or associated hypercalcaemia are not fully understood yet.

Methods: A systematic literature research including the six biggest databases for medical research has been used to identify all published case reports of SCFN. N = 206 publications has been identified containing n = 320 case reports. All cases have been classified into four subgroups (depending on reported serum-calcium-level): hypercalcaemia, normocalcaemia, hypocalcaemia or no information given. Reported maternal factors, birth characteristics, details about SCFN, diagnostics, therapy and long-term observations have been extracted from publications.

Results: This is the first systematic literature research that summed up all published cases of SCFN from 1948 up to 2018. Information about serum calcium level was given in 64.3% of the cases. From those, the majority showed hypercalcaemia (70.5%) (normocalcaemia 25.1%, hypocalcemia 4.3%). 89.3% of newborns with hypercalcaemia showed suppressed levels of the parathormone. Maternal gestational diabetes, maternal hypertensive diseases during pregnancy, macrosomia (> 4000g), asphyxia and therapeutic hypothermia are risk factors for SCFN. Histological findings showed a granulomatous inflammation in 98% of cases.

Conclusion: We identified that maternal, birth characteristics and therapeutic measures are probably risk factors for SCFN. These risk factors should be taken into account within the care of neonates.

Background: A series of noxae can evoke the termination of nephron formation in preterm and low birth weight babies. This results in oligonephropathy with severe consequences for health in the later life. Although the clinical parameters have been extensively investigated, little is known about the initial damage. Previous pathological findings indicate the reduction in width of the nephrogenic zone and the lack of S-shaped bodies. Current morphological investigations suggest that due to the mutual patterning beside the forming nephron, also its structural neighbors, particularly the interjacent interstitium, must be affected. However, beside the findings on integrative and mastering functions, systematic microanatomical data explaining the configuration of the interstitium at the developing nephron in the fetal kidney during advanced pregnancy is not available. Therefore, this work explains the typical features.

Results: The generated data depicts that the progenitor cells, nephrogenic niche, pretubular aggregate, and mesenchymal-to-epithelial transition are restricted to the subcapsular interstitium. During the proceeding development, only the distal pole of the renal vesicles and comma- and S-shaped bodies stays in further contact with it. The respective proximal pole is positioned opposite the peritubular interstitium at the connecting tubule of an underlying but previously formed nephron. The related medial aspect faces the narrow peritubular interstitium of a collecting duct (CD) ampulla first only at its tip, then at its head, conus, and neck, and finally at the differentiating CD tubule. The lateral aspect starts at the subcapsular interstitium, but then it is positioned along the wide perivascular interstitium of the neighboring ascending perforating radiate artery. When the nephron matures, the interstitial configuration changes again.

Conclusions: The present investigation illustrates that the interstitium at the forming nephron in the fetal kidney consists of existing, transient, stage-specific, and differently far matured compartments. According to the developmental needs, it changes its shape by formation, degradation, fusion, and rebuilding.

In the neonatal lung, exposure to both prenatal and early postnatal risk factors converge into the development of injury and ultimately chronic disease, also known as bronchopulmonary dysplasia (BPD). The focus of many studies has been the characteristic inflammatory responses provoked by these exposures. Here, we review the relationship between immaturity and prenatal conditions, as well as postnatal exposure to mechanical ventilation and oxygen toxicity, with the imbalance of pro- and anti-inflammatory regulatory networks. In these conditions, cytokine release, protease activity, and sustained presence of innate immune cells in the lung result in pathologic processes contributing to lung injury. We highlight the recruitment and function of myeloid innate immune cells, in particular, neutrophils and monocyte/macrophages in the BPD lung in human patients and animal models. We also discuss dissimilarities between the infant and adult immune system as a basis for the development of novel therapeutic strategies.

Human milk contains more than 150 different oligosaccharides, which together are among to the quantitatively predominant solid components of breast milk. The oligosaccharide content and composition of human milk show large inter-individual differences. Oligosaccharide content is mostly influenced by genetic variants of the mother's secretor status. Oligosaccharides in human milk are utilized by infants' intestinal bacteria, affecting bacterial composition and metabolic activity. Maternal secretor status, and respective differing fucosylated oligosaccharide content, has been associated both with reduced and increased risk of infection in different populations of breastfed infants, possibly due to environmental conditions and the infant's genotype. There are no safety concerns regarding the addition of previously approved oligosaccharides to infant formula; however, no firm conclusions can be drawn about clinically relevant benefits either. Therefore, infant formulas with synthetic oligosaccharide additives are currently not preferentially recommended over infant formulas without such additives. We consider the use of terms such as "human milk oligosaccharides" and corresponding abbreviations such as "HMO" in any advertising of infant formula to be an inappropriate idealization of infant formula. Manufacturers should stop this practice, and such marketing practices should be prevented by responsible supervisory authorities. Pediatricians should inform families that infant formulas supplemented with synthetic oligosaccharides do not resemble the complex oligosaccharide composition of human milk.

Background: Chronic kidney disease (CKD) is a global burden affecting both children and adults. Novel imaging modalities hold great promise to visualize and quantify structural, functional, and molecular organ damage. The aim of the study was to visualize and quantify murine renal vasculature using label-free raster scanning optoacoustic mesoscopy (RSOM) in explanted organs from mice with renal injury.

Material and methods: For the experiments, freshly bisected kidneys of alpha 8 integrin knock-out (KO) and wildtype mice (WT) were used. A total of n=7 female (n=4 KO, n=3 WT) and n=6 male animals (n=2 KO, n=4 WT) aged 6 weeks were examined with RSOM optoacoustic imaging systems (RSOM Explorer P50 at SWL 532nm and/or ms-P50 imaging system at 532 nm, 555 nm, 579 nm, and 606 nm). Images were reconstructed using a dedicated software, analyzed for size and vascular area and compared to standard histologic sections.

Results: RSOM enabled mapping of murine kidney size and vascular area, revealing differences between kidney sizes of male (m) and female (f) mice (merged frequencies (MF) f vs. m: 52.42±6.24 mm² vs. 69.18±15.96 mm², p=0.0156) and absolute vascular area (MF f vs. m: 35.67±4.22 mm² vs. 49.07±13.48 mm², p=0.0036). Without respect to sex, the absolute kidney area was found to be smaller in knock-out (KO) than in wildtype (WT) mice (WT vs. KO: MF: p=0.0255) and showed a similar trend for the relative vessel area (WT vs. KO: MF p=0.0031). Also the absolute vessel areas of KO compared to WT were found significantly different (MF p=0.0089). A significant decrease in absolute vessel area was found in KO compared to WT male mice (MF WT vs. KO: 54.37±9.35 mm² vs. 34.93±13.82 mm², p=0.0232). In addition, multispectral RSOM allowed visualization of oxygenated and deoxygenated parenchymal regions by spectral unmixing.

Conclusion: This study demonstrates the capability of RSOM for label-free visualization of differences in vascular morphology in ex vivo murine renal tissue at high resolution. Due to its scalability optoacoustic imaging provides an emerging modality with potential for further preclinical and clinical imaging applications.

Different gastrointestinal pathogens cause diarrhea which is a very common problem in children aged under 5 years. Among bacterial pathogens, Shigella is one of the main causes of diarrhea among children, and it accounts for approximately 11% of all deaths among children aged under 5 years. The case-fatality rates for Shigella among the infants and children aged 1 to 4 years are 13.9% and 9.4%, respectively. Shigella uses unique effector proteins to modulate intracellular pathways. Shigella cannot invade epithelial cells on the apical site; therefore, it needs to pass epithelium through other cells rather than the epithelial cell. After passing epithelium, macrophage swallows Shigella, and the latter should prepare itself to exhibit at least two types of responses: (I) escaping phagocyte and (II) mediating invasion of and injury to the recurrent PMN. The presence of PMN and invitation to a greater degree resulted in gut membrane injuries and greater bacterial penetration. Infiltration of Shigella to the basolateral space mediates (A) cell attachment, (B) cell entry, (C) evasion of autophagy recognition, (D) vacuole formation and and vacuole rapture, (E) intracellular life, (F) Shiga toxin, and (G) immune response. In this review, an attempt is made to explain the role of each factor in Shigella infection.