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Since the relatively recent regulatory approval for clinical use in both Europe and North America, 7-Tesla (T) MRI has been adopted for clinical practice at our institution. Based on this experience, this article reviews the unique features of 7-T MRI neuroimaging and addresses the challenges of establishing a 7-T MRI clinical practice. The underlying fundamental physics principals of high-field strength MRI are briefly reviewed. Scanner installation, safety considerations, and artifact mitigation techniques are discussed. Seven-tesla MRI case examples of neurologic diseases including epilepsy, vascular abnormalities, and tumor imaging are presented to illustrate specific applications of 7-T MRI. The advantages of 7-T MRI in conjunction with advanced neuroimaging techniques such as functional MRI are presented. Seven-tesla MRI produces more detailed information and, in some cases, results in specific diagnoses where previous 3-T studies were insufficient. Still, persistent technical issues for 7-T scanning present ongoing challenges for radiologists.

We investigated the hypothesis that increasing fMRI temporal resolution using a multiband (MB) gradient echo-echo planar imaging (GRE-EPI) pulse sequence provides fMRI language maps of higher statistical quality than those acquired with a traditional GRE-EPI sequence. This prospective study enrolled 29 consecutive patients receiving language fMRI prior to a potential brain resection for tumor, AVM, or epilepsy. A 4-min rhyming task was performed at 3.0 Tesla with a traditional GRE-EPI pulse sequence (TR = 2000, TE = 30, matrix = 64/100%, slice = 4/0, FOV = 24, slices = 30, time points = 120) and an additional MB GRE-EPI pulse sequence with an acceleration factor of 6 (TR = 333, TE = 30, matrix 64/100%, slice = 4/0, FOV = 24, time points = 720). Spatially filtered t statistical maps were generated. Volumes of interest (VOIs) were drawn around activations at Broca’s, dorsolateral prefrontal cortex, Wernicke’s, and the visual word form areas. The t value maxima were measured for the overall brain and each of the VOIs. A paired t test was performed for the corresponding traditional and MB GRE-EPI measurements. The mean age of subjects was 42.6 years old (18–75). Sixty-two percent were male. The average overall brain t statistic maxima for the MB pulse sequence (t = 15.4) was higher than for the traditional pulse sequence (t = 9.3, p = < .0001). This also held true for Broca’s area (p < 0.0001), Wernicke’s area (p < .0001), dorsolateral prefrontal cortex (p < .0001), and the visual word form area (p < .0001). A MB GRE-EPI fMRI pulse sequence employing high temporal resolution provides clinical fMRI language maps of greater statistical significance than those obtained with a traditional GRE-EPI sequence.

Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of chronic kidney disease and end-stage kidney disease in children. Increasing evidence points to critical roles for the urothelium in the developing urinary tract and in the genesis of CAKUTs. The involvement of the urothelium in patterning the urinary tract is supported by evidence that CAKUTs can arise as a result of abnormal urothelial development. Emerging evidence indicates that congenital urinary tract obstruction triggers urothelial remodelling that stabilizes the obstructed kidney and limits renal injury. Finally, the diagnostic potential of radiological findings and urinary biomarkers derived from the urothelium of patients with CAKUTs might aid their contribution to clinical care.

Hepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68ΔC) or N-terminal (Sam68ΔN) domains fails to bind CRTC2 or to stabilize CRTC2 protein, respectively, and transgenic Sam68ΔN mice recapitulate the blood-glucose and gluconeogenesis profile of Sam68-deficient mice. Hepatic Sam68 expression is also upregulated in patients with diabetes and in two diabetic mouse models, while hepatocyte-specific Sam68 deficiencies alleviate diabetic hyperglycemia and improves insulin sensitivity in mice. Thus, our results identify a role for Sam68 in hepatic gluconeogenesis, and Sam68 may represent a therapeutic target for diabetes., Hepatic gluconeogenesis is important for glucose homeostasis and a therapeutic target for type 2 diabetes. Here, the authors show that the RNA-binding adaptor protein Sam68 promotes the expression level of gluconeogenic genes and increases blood glucose levels by stabilizing the transcriptional coactivator CRTC2, while hepatic Sam68 deletion alleviates hyperglycemia in mice.

Identifying the determinants of reproductive success in small-scale societies is critical for understanding how natural selection has shaped human evolution and behavior. The available evidence suggests that status-accruing behaviors such as hunting and prosociality are pathways to reproductive success, but social egalitarianism may diminish this pathway. Here we introduce a mixed longitudinal/cross-sectional dataset based on 45 years of research with the Batek, a population of egalitarian rain forest hunter-gatherers in Peninsular Malaysia, and use it to test the effects of four predictors of lifetime reproductive success: (i) foraging return rate, (ii) sharing proclivity, (iii) cooperative foraging tendency, and (iv) kin presence. We found that none of these factors can explain variation in lifetime reproduction among males or females. We suggest that social egalitarianism, combined with strikingly low infant and juvenile mortality rates, can mediate the pathway between foraging, status-accruing behavior, and reproductive success. Our approach advocates for greater theoretical and empirical attention to quantitative social network measures, female foraging, and fitness outcomes.

While the $S_3$ scalar leptoquark presents a possible tree-level explanation of the $b \to s \ell \ell$ flavour anomalies, it suffers from two conceptual problems which are often disregarded by model-builders. Firstly, the quantum numbers of the $S_3$ allow for a renormalisable diquark operator that would trigger rapid proton decay unless its coupling were tuned away. Secondly, one expects the leptoquark to have generic couplings to leptons, which require tuning to avoid stringent experimental bounds on lepton flavour violation. By gauging a $U(1)$ current that acts as $L_\mu - L_\tau$ on the Standard Model (SM) fermions, and under which the leptoquark has charge $-1$, one can remedy both these problems. The additional $U(1)$, which is spontaneously broken at some high scale, is associated with a massive $Z^\prime$ gauge boson and a scalar SM singlet $\Phi$, which play no direct role in mediating the anomalous $B$ meson decays. By computing one- and two-loop mass corrections, we show that this pair of particles can be hidden away at much higher mass scales without destabilising either the Higgs or the leptoquark masses. The only low-energy relic of gauging $L_\mu - L_\tau$ is thus the accidental global symmetry structure of the lagrangian. On the other hand, we find quite generally that an $S_3$ leptoquark that mediates the $b \to s \ell \ell$ anomalies cannot be much heavier than a few TeV without itself inducing large Higgs mass corrections.

Pediatric neuroimaging is a complex and specialized field that uses magnetic resonance (MR) imaging as the workhorse for diagnosis. MR protocols should be tailored to the specific indication and reviewed by the supervising radiologist in real time. Targeted advanced imaging sequences can be added to provide information regarding tissue microstructure, perfusion, metabolism and function. In part 2 of this review, we highlight the utility of advanced imaging techniques for superior evaluation of pediatric neurologic disease. We focus on the following techniques, with clinical examples: phase-contrast imaging, perfusion-weighted imaging, vessel wall imaging, diffusion tensor imaging, task-based functional MRI and MR spectroscopy.

The clinical and financial impact of chronic kidney disease (CKD) is significant, while its progression and prognosis is variable and often poor. Studies using the megabladder (mgb−/−) model of CKD show that renal urothelium plays a key role in modulating early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical, and molecular characterization of Upk1bRFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/asymmetric membrane unit (AUM) formation, and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence that Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis, and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in normal development and pathogenesis of the urinary tract and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression.

G protein-coupled receptors (GPCRs) have important functions in both innate and adaptive immunity, with the capacity to bridge interactions between the two arms of the host responses to pathogens through direct recognition of secreted microbial products or the by-products of host cells damaged by pathogen exposure. In the mid-1990s, a large group of intracellular proteins was discovered, the regulator of G protein signaling (RGS) family, whose main, but not exclusive, function appears to be to constrain the intensity and duration of GPCR signaling. The R4/B subfamily--the focus of this review--includes RGS1-5, 8, 13, 16, 18, and 21, which are the smallest RGS proteins in size, with the exception of RGS3. Prominent roles in the trafficking of B and T lymphocytes and macrophages have been described for RGS1, RGS13, and RGS16, while RGS18 appears to control platelet and osteoclast functions. Additional G protein independent functions of RGS13 have been uncovered in gene expression in B lymphocytes and mast cell-mediated allergic reactions. In this review, we discuss potential physiological roles of this RGS protein subfamily, primarily in leukocytes having central roles in immune and inflammatory responses. We also discuss approaches to target RGS proteins therapeutically, which represents a virtually untapped strategy to combat exaggerated immune responses leading to inflammation.

Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.

Most men newly diagnosed with prostate cancer will undergo local treatment with prostatectomy, radiation, or tissue ablation. A small percentage of these men will develop a rectourethral fistula, a complicated disease that requires a multidisciplinary approach to management. Diagnosis is typically made with a careful history and physical exam with endoscopy and select imaging recommended in all patients. Fistulas resulting from prostatectomy, radiation, or tissue ablative technology are approached differently due to local tissue changes following therapy. Post-radiation and thermal ablation fistulas have a lower fistula closure rate due to the deleterious effect of the primary treatment on local tissue. It is imperative that the patient understands the complexity of treatment and sets reasonable goals for treatment.

Context Green infrastructure may improve water quality and mitigate flooding in forest-urban watersheds, but reliably quantifying all benefits is challenging because most land cover maps depend on moderate- to low-resolution data. Complex and spatially heterogeneous landscapes that typify forest-urban watersheds are not fully represented with these types of data. Hence important questions concerning how green infrastructure influences water quality and quantity at different spatial scales remain unanswered. Objectives Demonstrate the feasibility of creating novel high-resolution land cover maps across entire watersheds and highlight deficiencies of standard land cover products. Methods We used object-based image analysis (OBIA) to create high-resolution (0.5 m) land cover maps and detect tree canopy overlapping impervious surfaces for a representative forest-urban watershed in Duluth, MN, USA. Unbiased estimates of accuracy and area were calculated and compared with similar metrics for the 30-m National Land Cover Database (NLCD). Results Mapping accuracies for the high-resolution land cover and canopy overlap maps were ~90 %. Error-adjusted estimates of area indicated that impervious surfaces comprised ~21 % of the watershed, tree canopy overlapped ~10 % of impervious surfaces, and that three high-resolution land cover classes differed significantly from similar NLCD classes. Conclusions OBIA can efficiently generate high-resolution land cover products of entire watersheds that are appropriate for research and inclusion in the decision-making process of managers. Metrics derived from these products will likely differ from standard land cover maps and may produce new insights, especially when considering the unprecedented opportunity to evaluate fine-scale spatial heterogeneity across watersheds.

Objectives To prospectively evaluate the new medical device Transurethral Suprapubic endo-Cystostomy (T-SPeC®), used for suprapubic catheter (SPC) placement via the transurethral (inside-to-out) approach, and examine the 30-day outcomes in the first US series. Methods IRB approval was obtained for this prospective study. We evaluated the first 114 consecutive cases of SPC placement using the T-SPeC® device by a single surgeon at in a 20-month period. We excluded patients who underwent alternative approaches to suprapubic catheter placement including open abdominal approach (12) and percutaneous approach (5). Preoperative patient demographics, operative detail, success rate and 30-day complication rate were recorded. Results We successfully placed an 18 Fr suprapubic catheter using the T-SPeC® device in 98.2 % of patients. During the procedure, the capture housing was missed twice. The mean patient age was 56.6, BMI 29.4 kg/m2, skin to bladder distance 6.7 cm and operative time 3.6 min. There were 12 postoperative complications within 30 days of the procedure including urinary tract infections (6), SPC exit site infection (2), SPC blockage (2) and catheter expulsion (2). There were no Clavien–Dindo grade III–IV complications such as re-operation, small bowel injury, hemorrhage or death. Conclusion The T-SPeC® device is a novel, simple, accurate and minimally invasive device for SPC insertion from an inside-to-out approach. Our prospective study demonstrates that the T-SPeC® device can be placed safely and efficiently in a variety of patients with a need for urinary drainage.

Despite 100 years of study, the theories of cerebrospinal fluid (CSF) formation and absorption remain controversial. Measuring CSF flow through the aqueduct using magnetic resonance imaging (MRI) provides a unique insight into the physiology of CSF hydrodynamics. The published data in adults tend to refute rather than support the prevailing theories of CSF flow. There are limited data regarding this metric in children. This paper seeks to measure the aqueduct flow in normal and hydrocephalic children to help formulate a more complete theory of CSF flow. Twenty-four children with communicating hydrocephalus aged from 4 months to 16 years underwent MRI flow quantification of the aqueduct measuring the net flow. The patients were compared to 19 controls. The controls revealed two different flow patterns: (1) an infantile pattern characterized by flow directed into the ventricular system and (2) a mature pattern with flow directed out of the ventricles, similar to the published findings in adults. In infants with communicating hydrocephalus, the aqueduct flow changed direction but was of similar magnitude compared with the controls (p = 0.001). In the older hydrocephalic children, the flow was elevated 7-fold, but the direction was unchanged compared to the controls (p = 0.002). There is an abrupt change in the aqueduct CSF flow pattern at the age of 2 years from an infantile pattern to a mature pattern. These findings together with the findings in hydrocephalic children do not support the current theories of CSF hydrodynamics. A new theory of CSF circulation based on capillary absorption is presented.

Congenital obstructive nephropathy is the leading cause of chronic renal disease in children. As a result, it represents a tremendous societal burden in terms of morbidity and mortality, as well as in health care expenses of caring for children with chronic kidney disease and end-stage renal disease. The various diagnostic, prognostic, and therapeutic challenges associated with congenital obstructive nephropathy highlight the importance of developing effective experimental models for studying this disease process. In this review, we define the clinical entity that is congenital obstructive nephropathy, outline the current standards of diagnosis and care, and discuss the utilization of current experimental models designed to help clarify some of the clinical conundrums associated with this important disease.

Prune belly syndrome (PBS) is a congenital anomaly characterized by the clinical triad of lax abdominal musculature, bilateral cryptorchidism, and abnormalities of the kidney and urinary tract. Previous reports of malignancy in patients with PBS have been limited to germ cell tumors. Hepatoblastoma (HBL) is the most common hepatic malignancy of childhood, affecting approximately 100 children each year in the USA. We describe a set of 4 pediatric patients with PBS and HBL. All individuals were born after 2002. These subjects lacked genetic, natal, or environmental factors known to confer risk of HBL. The occurrence of PBS and HBL in these patients constitutes a novel potential association.

The initial identification of glucagon as a counter-regulatory hormone to insulin revealed this hormone to be of largely singular physiological and pharmacological purpose. Glucagon agonism, however, has also been shown to exert effects on lipid metabolism, energy balance, body adipose tissue mass and food intake. The ability of glucagon to stimulate energy expenditure, along with its hypolipidemic and satiating effects, in particular, make this hormone an attractive pharmaceutical agent for the treatment of dyslipidemia and obesity. Studies that describe novel preclinical applications of glucagon, alone and in concert with glucagon-like peptide 1 agonism, have revealed potential benefits of glucagon agonism in the treatment of the metabolic syndrome. Collectively, these observations challenge us to thoroughly investigate the physiology and therapeutic potential of insulin's long-known opponent.

This study evaluates the impact of pediatric uninary tract infection (UTI)s on the economy and inpatient healthcare utilization in the USA. A retrospective analysis of patient demographics and hospital economics was performed on children less than 18 years of age admitted with a UTI between 2000 and 2006 using the Healthcare Cost and Utilization Project Kids’ Inpatient Database. Our results were stratified as follows. Hospital admissions—nearly 50,000 children/year were admitted with a UTI. Pediatric UTIs represented 1.8% of all pediatric hospitalizations. Seventy-three percent of patients were female and 40% were under 1 year of age. Payer information—from 2000 to 2006, pediatric insurance coverage shifted from the private sector to the public sector. Hospital cost—in 2000, estimated hospital costs for UTIs were $2,858 per hospitalization and rose to $3,838 by 2006. Mean hospital charges increased from $6,279 to $10,489 per stay. By 2006, aggregate hospital charges exceeded $520 million. Our results indicate that UTIs are among the most common pediatric admission diagnoses. Hospitalization is more common in females and younger children. Since 2000, hospital charges for UTIs increased disproportionately to hospital costs. Over time, more children hospitalized with a UTI depend on public agencies to cover healthcare expense. More efforts are needed to evaluate cost-effective strategies for evaluation and treatment of UTIs.

Renal agenesis/adysplasia is the leading etiology of end stage renal disease in children. The etiology for renal agenesis/adysplasia has not been identified. The purpose of the present study was to determine if renal agenesis/adysplasia occur in a familial pattern. Twenty seven cases of bilateral renal agenesis/adysplasia were identified by review of autopsy records, and four were excluded. A male excess of 2.8:1 was noted with a mean gestation of 35 weeks. Prenatal and family histories were obtained on 11/23 families. Potential embryologic stressors were identified in 8/11 pregnancies. Thirty-four 1st and 2nd degree relatives from five families participated in a renal ultrasound exam. An increased prevalence of congenital renal anomalies was identified in the relatives of index patients with bilateral renal agenesis/adysplasia (14.7%) compared to controls (2.2%), with a recurrence risk of 6.2 for 1st degree relatives. The most frequently identified renal anomalies in the family members were solitary kidneys and duplicated collecting systems. The increased prevalence of a range of renal anomalies within affected families raises the possibility that isolated renal malformations result from unidentified gene-environment interactions.

The development and initial psychometric studies for the Ohio Youth Problems, Functioning, and Satisfaction Scales (Ohio Scales) are described. The Ohio Scales were developed to be practical yet rigorous, multi-content, multi-source measures of outcome for children and adolescents receiving mental health services. Initial studies suggest that the Ohio Scales are promising (reliable, valid, and sensitive to change) measures that can be used to track the effectiveness of mental health interventions for youth with serious emotional disorders. Additional studies are warranted to expand the situations and populations within which the scales are valid.