Prolonging nephrogenesis in preterm infants: a new approach for prevention of kidney disease in adulthood?

Chronic kidney disease represents a dramatic worldwide resourceconsuming problem. This problem is of increasing importance even in preterm infants, since nephrogenesis may go on only for a few weeks (4 to 6 weeks) after birth. Recent literature focusing on traditional regenerative medicine does not take into account the presence of a high number of active endogenous stem cells in the preterm kidney, which represents a unique opportunity for starting regenerative medicine in the perinatal period. Pluripotent cells of the blue strip have the capacity to generate new nephrons, improving kidney function in neonates and potentially protecting them from developing chronic kidney disease and end-stage renal disease in adulthood. There is a marked interindividual neonatal variability of nephron numbers. Moreover, the renal stem/progenitor cells appear as densely-packed small cells with scant cytoplasm, giving rise to a blue-appearing strip in hematoxylin-eosin–stained kidney sections (“the blue strip”). There are questions concerning renal regenerative medicine: among preliminary data, the simultaneous expression of Wilms tumor 1 and thymosin β4 in stem/progenitor cells of the neonatal kidney may bring new prospects for renal regeneration applied to renal stem cells that reside in the kidney itself. A potential approach could be to prolong the 6 weeks of postnatal renal growth of nephrons or to accelerate the growth of nephrons during the 6 weeks or both. Considering what we know today about perinatal programming, this could be an important step for the future to reduce the incidence and global health impact of chronic kidney disease

Assisted Reproductive Technologies: A New Player in the Foetal Programming of Childhood and Adult Diseases?

Assisted reproductive technology (ART) is an emerging field in medicine that incorporates complex procedures and has profound ethical, moral, social, religious, and economic implications not just for the individuals who have access to this method but also for society. In this narrative review, we summarise multiple aspects of ART procedures and the possible consequences on the mother and newborn. Moreover, we provide an overview of the possible long-term consequences of ART procedures on the health of newborns, although longitudinal evidence is particularly scant. Users should be informed that ART procedures are not risk-free to prepare them for the possible negative outcomes that may occur in the perinatal period or even in childhood and adulthood. Indeed, risk estimates point to increased liability for major nonchromosomal birth defects; cardiovascular, musculoskeletal, and urogenital (in male newborns) defects; and any other birth defects. Less certainty is present for the risk of neuropsychiatric sequelae in children conceived through ART. Thus, its application should be accompanied by adequate counselling and psychological support, possibly integrated into specific multidisciplinary clinical programmes

Metabolic reprogramming of immune cells following vaccination: from metabolites to personalized vaccinology

Identifying metabolic signatures induced by the immune response to vaccines allows to discriminate vaccinated from non-vaccinated subjects and decipher the molecular mechanisms associated with the host immune response. This review illustrates and discusses the results of metabolomics-based studies on the innate and adaptive immune response to vaccines, long-term functional reprogramming (immune memory), and adverse reactions. Glycolysis is not overexpressed by vaccines, suggesting that the immune cell response to vaccinations does not require rapid energy availability as that is necessary during an infection. Vaccines strongly impact lipids metabolism, including saturated or unsaturated fatty acids, inositol phosphate, and cholesterol. Cholesterol is strategic for synthesizing 25-hydroxycholesterol in activated macrophages and dendritic cells and stimulates the conversion of macrophages and T cells in M2 macrophage and Treg, respectively. In conclusion, the large-scale application of metabolomics enables the identification of candidate predictive biomarkers of vaccine efficacy/tolerability

Cranberry in children: prevention of recurrent urinary tract infections and review of the literature

Urinary tract infections (UTI) are common in childhood. In 30-50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), neurogenic bladder (NB), previous cystitis or pyelonephritis and malformative uropathies. To reduce the likelihood of UTI, antibiotic prophylaxis has been regarded as the therapeutic standard for many years. However, the disadvantage of long-term antibiotic therapy is the potential for development of collateral effects and resistant organisms in the host. Such reasons have induced scientists to search for alternative modalities of UTI prevention and have contributed to determining the increasing desire for "naturalness" of the population and preventing excessive medication. The use of cranberry fulfils these needs by potentially replacing or enhancing traditional procedures. The purpose of this study was to assess the effectiveness of cranberry in preventing UTI in pediatric populations. We searched Pubmed, the Cochrane Central Register of Controlled Trials and Internet. Cranberry in patients with previous UTI was evaluated in three studies, cranberry in patients with VUR in three studies and four studies analyzed the efficacy of cranberry in children with NB. In seven of nine studies cranberry had a significant effect in preventing UTI

Integrative Multiomics Approach to Skin: The Sinergy between Individualised Medicine and Futuristic Precision Skin Care?

The skin is a complex ecosystem colonized by millions of microorganisms, the skin microbiota, which are crucial in regulating not only the physiological functions of the skin but also the metabolic changes underlying the onset of skin diseases. The high microbial colonization together with a low diversity at the phylum level and a high diversity at the species level of the skin is very similar to that of the gastrointestinal tract. Moreover, there is an important communication pathway along the gut-brain-skin axis, especially associated with the modulation of neurotransmitters by the microbiota. Therefore, it is evident that the high complexity of the skin system, due not only to the genetics of the host but also to the interaction of the host with resident microbes and between microbe and microbe, requires a multi-omics approach to be deeply understood. Therefore, an integrated analysis, with high-throughput technologies, of the consequences of microbial interaction with the host through the study of gene expression (genomics and metagenomics), transcription (transcriptomics and meta-transcriptomics), and protein production (proteomics and meta-proteomics) and metabolite formation (metabolomics and lipidomics) would be useful. Although to date very few studies have integrated skin metabolomics data with at least one other 'omics' technology, in the future, this approach will be able to provide simple and fast tests that can be routinely applied in both clinical and cosmetic settings for the identification of numerous skin diseases and conditions. It will also be possible to create large archives of multi-omics data that can predict individual responses to pharmacological treatments and the efficacy of different cosmetic products on individual subjects by means of specific allotypes, with a view to increasingly tailor-made medicine. In this review, after analyzing the complexity of the skin ecosystem, we have highlighted the usefulness of this emerging integrated omics approach for the analysis of skin problems, starting with one of the latest 'omics' sciences, metabolomics, which can photograph the expression of the genome during its interaction with the environment

Pulmonary Tuberculosis in Children: A Forgotten Disease?

Even today, tuberculosis in childhood is a disease that is often undiagnosed and undertreated. In the absence of therapy with antituberculosis drugs, children in the first years of life have a high degree of severe forms and mortality. In these children, symptoms are often not very specific and can easily be confused with other diseases of bacterial, viral or fungal etiology, making diagnosis more difficult. Nevertheless, the introduction of new diagnostic techniques has allowed a more rapid identification of the infection. Indeed, Interferon gamma release assay (IGRA) is preferred to the Mantoux, albeit with obvious limitations in children aged <2 years. While the Xpert Mtb/RIF Ultra test is recommended as an initial diagnostic investigation of the gastric aspirate and/or stools in children with signs and symptoms of pulmonary tuberculosis. The drugs used in the treatment of susceptible and resistant TB are the same as those used in adults but doses and combinations are different in the pediatric age. In children, brief therapy is preferable in both the latent infection and the active disease, as a significant reduction in side effects is obtained

Metabolomics and fetal-neonatal nutrition: Between "not enough" and "too much"

Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases. © 1996-2013 MDPI AG

NGAL and metabolomics: The single biomarker to reveal the metabolome alterations in kidney injury

Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. Acute kidney injury (AKI) is one of a number of acute kidney diseases and consists of an abrupt decline in kidney function after an injury leading to functional and structural changes. The widespread availability of enabling technologies has accelerated the rate of novel biomarker discovery for kidney injury. The introduction of novel biomarkers in clinical practice will lead to better preventative and therapeutic interventions and to improve outcomes of critically ill patients. A number of biomarkers of functional change and cellular damage are under evaluation for early diagnosis, risk assessment, and prognosis of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the most promising biomarker of kidney injury; this protein can be measured by commercially available methods in whole blood, plasma, serum, and urine. Concomitantly, metabolomics appears to be a snapshot of the chemical fingerprints identifying specific cellular processes. In this paper, we describe the role of NGAL for managing AKI and the potential benefits deriving from the combined clinical use of urine NGAL and metabolomics in kidney disease

Should we definitively abandon prophylaxis for patent ductus arteriosus in preterm new-borns?

Although the prophylactic administration of indomethacin in extremely low-birth weight infants reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage, it does not appear to provide any long-term benefit in terms of survival without neurosensory and cognitive outcomes. Considering the increased drug-induced reduction in renal, intestinal, and cerebral blood flow, the use of prophylaxis cannot be routinely recommended in preterm neonates. However, a better understanding of the genetic background of each infant may allow for individualized prophylaxis using NSAIDs and metabolomics