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Probiotics have received significant attention within both the scientific and lay communities for their potential health-promoting properties, including the treatment or prevention of various conditions in children. In this article, we review the published data on use of specific probiotic strains for three common pediatric conditions: the prevention of urinary tract infections and antibiotic-associated diarrhea and the treatment of atopic dermatitis. Research into the utility of specific probiotic strains is of varying quality, and data are often derived from small studies and case series. We discuss the scientific merit of these studies, their overall findings regarding the utility of probiotics for these indications, issues in reporting of methods, and results from these clinical trials, as well as future areas of investigation., Impact: Review of data for commonly encountered diagnoses in the general pediatric population.Highlights gaps in the evidence and provides insight into new avenues of research.

Background Schistosoma haematobium, the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between S. haematobium and bladder cancer, the underlying mechanisms are poorly understood. S. haematobium oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia. These changes may be pre-carcinogenic events in the bladder. We hypothesized that the Interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE), an S. haematobium egg-secreted “infiltrin” protein that enters host cell nuclei to alter cellular activity, is sufficient to induce angiogenesis and urothelial hyperplasia. Methods: Mouse bladders injected with S. haematobium eggs were analyzed via microscopy for angiogenesis and urothelial hyperplasia. Endothelial and urothelial cell lines were incubated with recombinant IPSE protein or an IPSE mutant protein that lacks the native nuclear localization sequence (NLS-) and proliferation measured using CFSE staining and real-time monitoring of cell growth. IPSE’s effects on urothelial cell cycle status was assayed through propidium iodide staining. Endothelial and urothelial cell uptake of fluorophore-labeled IPSE was measured. Findings: Injection of S. haematobium eggs into the bladder triggers angiogenesis, enhances leakiness of bladder blood vessels, and drives urothelial hyperplasia. Wild type IPSE, but not NLS-, increases proliferation of endothelial and urothelial cells and skews urothelial cells towards S phase. Finally, IPSE is internalized by both endothelial and urothelial cells. Interpretation: IPSE drives endothelial and urothelial proliferation, which may depend on internalization of the molecule. The urothelial effects of IPSE depend upon its NLS. Thus, IPSE is a candidate pro-carcinogenic molecule of S. haematobium. Summary Schistosoma haematobium acts as a bladder carcinogen through unclear mechanisms. The S. haematobium homolog of IPSE, a secreted schistosome egg immunomodulatory molecule, enhances angiogenesis and urothelial proliferation, hallmarks of pre-carcinogenesis, suggesting IPSE is a key pro-oncogenic molecule of S. haematobium.

We sought to examine the literature reporting the effect of urinary tract infection (UTI) on non-schistosomiasis-related UBC (UBCNS) through a systematic review and meta-analysis. A predefined study protocol was developed according to PRISMA. Medline and Scopus were searched for all studies investigating exposure to UTI with UBCNS as the primary outcome. Potential studies were screened against eligibility criteria. Clinical heterogeneity was assessed and groups with more than two studies were evaluated by random effect meta-analysis. Study-level bias was assessed with the Newcastle–Ottawa Scale (NOS). In cases of substantial between study heterogeneity (I2 > 50%), predefined sensitivity and subgroup analyses were performed. Of 16 eligible studies, eight case–control studies spanning four decades and five countries were suitable for quantitative analysis. Main analysis favored exposure to UTI increasing risk of subsequent UBCNS (RR 1.33 [95% CI 1.14–1.55]). This effect was no longer statistically significant after excluding studies published prior to year 2000 and at high risk of bias. Between study heterogeneity was considerable for nearly all analyses and not reduced by predefined sensitivity or subgroup analyses. Exposure to UTI favors increased risk for UBCNS, particularly in men, but these effects were statistically insignificant when pooling data from the most recent and highest quality studies. These data do not support findings of previously published studies, that report on heterogenous populations with poor definitions of UTI and minimal control for important confounders. Results from previous studies should be viewed as hypothesis generating. This review highlights the need for higher quality investigation.

Introduction People with neuropathic bladder (NB) secondary to spinal cord injury (SCI) are at risk for multiple genitourinary complications, the most frequent of which is urinary tract infection (UTI). Despite the high frequency with which UTI occurs, our understanding of the role of urinary microbes in health and disease is limited. In this paper, we present the first prospective case study integrating symptom reporting, urinalysis, urine cultivation, and 16S ribosomal ribonucleic acid (rRNA) sequencing of the urine microbiome. Case presentation A 55-year-old male with NB secondary to SCI contributed 12 urine samples over an 8-month period during asymptomatic, symptomatic, and postantibiotic periods. All bacteria identified on culture were present on 16S rRNA sequencing, however, 16S rRNA sequencing revealed the presence of bacteria not isolated on culture. In particular, Burkholderia fungorum was present in three samples during both asymptomatic and symptomatic periods. White blood cells of ≥5-10/high power field and leukocyte esterase ≥2 on urinalysis was associated with the presence of symptoms. Discussion In this patient, there was a predominance of pathogenic bacteria and a lack of putative probiotic bacteria during both symptomatic and asymptomatic states. Urinalysis-defined inflammatory markers were present to a greater extent during symptomatic periods compared to the asymptomatic state, which may underscore a role for urinalysis or other inflammatory markers in differentiating asymptomatic bacteriuria from UTI in patients with NB. The finding of potentially pathogenic bacteria identified by sequencing but not cultivation, suggests a need for greater understanding of the relationships amongst bacterial species in the bacteriuric neuropathic bladder.

Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumour progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog (Shh)-expressing stem cells in basal urothelium. These carcinomas arise clonally from a single cell whose progeny aggressively colonize a major portion of the urothelium to generate a lesion with histological features identical to human carcinoma in situ. Shh-expressing basal cells within this precursor lesion become tumour-initiating cells, although Shh expression is lost in subsequent carcinomas. We thus find that invasive carcinoma is initiated from basal urothelial stem cells but that tumour cell phenotype can diverge significantly from that of the cancer cell of origin.

BACKGROUND: Robot-assisted surgery is widely adopted for many procedures but has not realized its full potential to date. Based on human motor control theories, the authors hypothesized that the dynamics of the master manipulators impose challenges on the motor system of the user and may impair performance and slow down learning. Although studies have shown that robotic outcomes are correlated with the case experience of the surgeon, the relative contribution of cognitive versus motor skill is unknown. This study quantified the effects of da Vinci Si master manipulator dynamics on movements of novice users and experienced surgeons and suggests possible implications for training and robot design. METHODS: In the reported study, six experienced robotic surgeons and ten novice nonmedical users performed movements under two conditions: teleoperation of a da Vinci Si Surgical system and freehand. A linear mixed model was applied to nine kinematic metrics (including endpoint error, movement time, peak speed, initial jerk, and deviation from a straight line) to assess the effects of teleoperation and expertise. To assess learning effects, t tests between the first and last movements of each type were used. RESULTS: All the users moved slower during teleoperation than during freehand movements (F(1,9343) = 345; p < 0.001). The experienced surgeons had smaller errors than the novices (F(1,14) = 36.8; p < 0.001). The straightness of movements depended on their direction (F(7,9343) = 117; p < 0.001). Learning effects were observed in all conditions. Novice users first learned the task and then the dynamics of the manipulator. CONCLUSIONS: The findings showed differences between the novices and the experienced surgeons for extremely simple point-to-point movements. The study demonstrated that manipulator dynamics affect user movements, suggesting that these dynamics could be improved in future robot designs. The authors showed the partial adaptation of novice users to the dynamics. Future studies are needed to evaluate whether it will be beneficial to include early training sessions dedicated to learning the dynamics of the manipulator.