Assessment of the Urinary Microbiome in Children Younger Than 48 Months.

BACKGROUND: The urinary tract was once thought to be sterile, and little is known about the urinary microbiome in children. This study aimed to examine the urinary microbiome of young children across demographic and clinical factors. METHODS: Children <48 months, undergoing a urinary catheterization for clinical purposes in the Pediatric Emergency Department were recruited and urine samples collected. Detailed demographic and clinical information were recorded. Urine samples underwent DNA extraction and 16S ribosomal RNA gene sequencing, urinalysis and urine culture. RESULTS: Eighty-five children were included; a urinary microbiome was identified in every child. Nine children had Escherichia coli urinary tract infections (UTIs) identified. Those with UTIs had a significantly decreased alpha diversity (t test, P < 0.001) and the composition of the microbiome clustered separately (P = 0.001) compared with those without UTIs. CONCLUSIONS: A urinary microbiome was identified in every child, even neonates. Differences in microbiome diversity and composition were observed in patients with a standard culture positive UTI. The urinary microbiome has just begun to be explored, and the implications on long-term disease processes deserve further investigation.

Diagnosis of D-Bifunctional Protein Deficiency through Whole-Genome Sequencing: Implications for Cost-Effective Care.

D-Bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe disorder of peroxisomal fatty acid oxidation. Nonspecific clinical features may contribute to diagnostic challenges. We describe a newborn female with infantile-onset seizures and nonspecific mild dysmorphisms who underwent extensive genetic workup that resulted in the detection of a novel homozygous mutation (c.302+1_4delGTGA) in the HSD17B4 gene, consistent with a diagnosis of D-bifunctional protein deficiency. By comparing the standard clinical workup to diagnostic analysis performed through research-based whole-genome sequencing (WGS), which independently identified the causative mutation, we demonstrated the ability of genomic sequencing to serve as a timely and cost-effective diagnostic tool for the molecular diagnosis of apparent and occult newborn diseases. As genomic sequencing becomes more available and affordable, we anticipate that WGS and related omics technologies will eventually replace the traditional tiered approach to newborn diagnostic workup.

Five strategies for accelerating the war on cancer in an era of budget deficits.

In recent years, the National Institutes of Health's largest institute, the National Cancer Institute (NCI), has adapted to difficult economic conditions by leveraging its robust infrastructure -- which includes risk factor surveillance and population monitoring, research centers (focused on basic, translation, clinical, and behavioral sciences), clinical trials and health care research networks, and rigorously validated statistical models -- to maximize the impact of scientific progress on the public health. To continue advancement and realize the opportunity of significant, population-level changes in cancer mortality, the NCI recommends that five national-level actions be taken: (1) significantly increase enrollment of Medicare patients into cancer clinical trials through adequate physician reimbursement, (2) increase NCI/Centers for Medicare and Medicaid Services collaboration on clinical trials research to evaluate the therapeutic efficacy of anticancer drugs, (3) establish a national outcomes research demonstration project to test strategies for measuring and improving health care quality and provide an evidence base for public policy, (4) leverage existing tobacco-control collaborations and possible new authorities at the U.S. Food and Drug Administration to realize the outstanding health gains possible from a reduction in tobacco use, and (5) increase colorectal cancer screening rates though intensified collaboration between federal agencies working to address barriers to access and use of screening. These cost-effective strategies provide the opportunity for extraordinary results in an era of budget deficits. Of the chronic diseases, cancer has the strongest national research infrastructure that can be leveraged to produce rapid results to inform budget prioritization and public policy, as well as mobilize new projects to answer critical public health questions.

Response to: "Rescuing the NIH before it is too late".

We, the directors of the 27 NIH institutes and centers, wanted to respond to the points made by Andrew Marks in his recent editorial. While we appreciate that the scientific community has concerns, the current initiatives and directions of the NIH have been developed through planning processes that reflect openness and continued constituency input, all aimed at assessing scientific opportunities and addressing public health needs.