The Rat Genome Database (RGD) facilitates genomic and phenotypic data integration across multiple species for biomedical research.

Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions.

Prospective study of enhanced recovery after surgery protocol in children undergoing reconstructive operations.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a set of peri-operative strategies to increase speed of recovery. ERAS is well established in adults but has not been well studied in children. OBJECTIVE: The purpose of the current study was to establish the safety and efficacy of an ERAS protocol in pediatric urology patients undergoing reconstructive operations. It was hypothesized that ERAS would reduce length of stay and decrease complications when compared with historical controls. STUDY DESIGN: Institutional Review Board approval was obtained to prospectively enroll patients aged <18 years if they had undergone urologic reconstruction that included a bowel anastomosis. ERAS included: no bowel preparation, administration of pre-operative oral carbohydrate liquid, avoidance of opioids, regional anesthesia, laparoscopy when feasible, no postoperative nasogastric tube, early feeding, and early removal of intravenous fluids (IVF). Recent (2009-2014) historical controls were propensity matched in a 2:1 ratio on age, sex, ventriculoperitoneal shunt status and whether the patient was undergoing bladder augmentation. Outcomes were protocol adherence, length of stay (LOS), emergency department (ED) visits, re-admission within 30 days, re-operations and adverse events occurring within 90 days of surgery. RESULTS: A total of 26 historical and 13 ERAS patients were included. Median ages were 10.4 (IQR 8.0-12.4) and 9.9 years (IQR 9.1-11), respectively (P = 0.94) (see Summary Table). There were no significant between-group differences in prior abdominal surgery (38% vs 62%), rate of augmentation (88% vs 92%) or primary diagnosis of spina bifida (both 62%). ERAS significantly improved use of pre-operative liquid load (P < 0.001), avoidance of opioids (P = 0.046), early discontinuation of IVF (P < 0.001), and early feeding (P < 0.001). Protocol adherence improved from 8/16 (IQR 4-9) historically to 12/16 (IQR 11-12) after implementation of ERAS. LOS decreased from 8 days to 5.7 days (P = 0.520). Complications of any grade per patient decreased from 2.1 to 1.3 (OR 0.71, 95% CI 0.51-0.97). There were fewer complications per patient across all grades with ERAS. No differences were seen in emergency department (ED) visits, re-admissions and re-operations. DISCUSSION: Implementation improved consistency of care delivered. Tenets of ERAS that appeared to drive improvements included maintenance of euvolemia through avoidance of excess fluids, multimodal analgesia, and early feeding. CONCLUSION: ERAS decreased length of stay and 90-day complications after pediatric reconstructive surgery without increased re-admissions, re-operations or ED visits. A multicenter study will be required to confirm the potential benefits of adopting ERAS.

Genitourinary and gastrointestinal co-morbidities in children: The role of neural circuits in regulation of visceral function.

OBJECTIVE: Pediatric lower urinary tract dysfunction (LUTD) is a common problem in childhood. Lower urinary tract symptoms in children include overactive bladder, voiding postponement, stress incontinence, giggle incontinence, and dysfunctional voiding. Gastrointestinal co-morbidities, including constipation or fecal incontinence, are commonly associated with lower urinary tract (LUT) symptoms in children, often reaching 22-34%. This review summarized the potential mechanisms underlying functional lower urinary and gastrointestinal co-morbidities in children. It also covered the current understanding of clinical pathophysiology in the pediatric population, anatomy and embryological development of the pelvic organs, role of developing neural circuits in regulation of functional co-morbidities, and relevant translational animal models. MATERIALS AND METHODS: This was a non-systematic review of the published literature, which summarized the available clinical and translational studies on functional urologic and gastrointestinal co-morbidities in children, as well as neural mechanisms underlying pelvic organ 'cross-talk' and 'cross-sensitization'. RESULTS: Co-morbidity of pediatric lower urinary and gastrointestinal dysfunctions could be explained by multiple factors, including a shared developmental origin, close anatomical proximity, and pelvic organ 'cross-talk'. Daily physiological activity and viscero-visceral reflexes between the lower gastrointestinal and urinary tracts are controlled by both autonomic and central nervous systems, suggesting the dominant modulatory role of the neural pathways. Recent studies have provided evidence that altered sensation in the bladder and dysfunctional voiding can be triggered by pathological changes in neighboring pelvic organs due to a phenomenon known as pelvic organ 'cross-sensitization'. Cross-sensitization between pelvic organs is thought to be mainly coordinated by convergent neurons that receive dual afferent inputs from discrete pelvic organs. Investigation of functional changes in nerve fibers and neurons sets certain limits in conducting appropriate research in humans, making the use of animal models necessary to uncover the underlying mechanisms and for the development of novel therapeutic approaches for long-term symptomatic treatment of LUTD in the pediatric population. CONCLUSION: Pediatric LUTD is often complicated by gastrointestinal co-morbidities; however, the mechanisms linking bladder and bowel dysfunctions are not well understood. Clinical studies have suggested that therapeutic modulation of one system may improve the other system's function. To better manage children with LUTD, the interplay between the two systems, and how co-morbid GI and voiding dysfunctions can be more specifically targeted in pediatric clinics need to be understood.

Inter-rater reliability of the APD, SFU and UTD grading systems in fetal sonography and MRI.

INTRODUCTION: Antenatal hydronephrosis (ANH) is frequently detected on screening obstetric ultrasonography. Common ANH grading systems include the anterior-posterior diameter (APD) and the Society for Fetal Urology (SFU) grading system. Recent developments in the management of ANH include the use of fetal magnetic resonance imaging (MRI), and a new grading system - Urinary Tract Dilation (UTD). This study reviewed patients who underwent fetal MRI and ultrasound, and compared the grading systems across these imaging modalities. MATERIALS AND METHODS: Patients who underwent paired fetal MRI and ultrasound studies between January 2012 and January 2014 were included. Two pediatric urologists and a pediatric radiologist reviewed the studies. Data collected included APD, SFU grade, and UTD grade. Fleiss' kappa statistic determined the inter-rater reliability (IRR) of the SFU and UTD grading within each imaging modality. Intra-class correlation assessed the consistency of the APD measurements. RESULTS: Forty-seven patients and 88 renal units were evaluated. Median gestational age was 22 weeks. Kappa values of the SFU grading system indicated fair IRR for ultrasound imaging and moderate IRR for MRI imaging, while the UTD grading system reached moderate IRR for both. The IRR of the SFU grading system was improved with the use of MRI, while the UTD grading system was no different. The APD intraclass correlation coefficient improved significantly when measured by MRI. As the ultrasound SFU grade increased, the odds of the MRI SFU grade being scored higher increased by a factor of 3.7. There was no difference between ultrasound and MRI when using the UTD grading system. DISCUSSION: This study was the first to assess the UTD system in a cohort of patients who underwent paired ultrasound and MRI studies. The results suggested that the UTD system might improve IRR, compared with the SFU system. The use of fetal MRI may improve the IRR of the SFU grading system. It also found that the proportion of SFU grades was affected by the imaging modality, raising the possibility that MRI 'overcalls' the SFU grade, compared with ultrasound. This difference was not observed using the UTD grading system. The most important limitation was the selection bias favoring complex pathology with severe ANH diagnosed at an early gestational age. CONCLUSIONS: In this unique cohort, the UTD system improved IRR when compared to the SFU grading system. Fetal MRI improved the IRR of the SFU grading system, and improved the APD intraclass correlation. The SFU grading was likely to be higher when assessed by MRI vs ultrasound, but the UTD grade was not affected by the imaging modality.

Study of clitoral hood anatomy in the pediatric population.

INTRODUCTION AND AIMS: Pediatric female genitalia size and morphology have not previously been well described. The aims of this study were to create a standard reference for the anterior vulval structures, and examine the relationship between the clitoral hood and labia minora. METHOD: Female patients between 0 and 16 years of age, and with normal external genitalia had the following measurements taken: length of clitoral hood, length of sides of clitoral hood, clitoral diameter, apex of clitoral hood to base of pubic symphysis, apex of clitoral hood to urethral orifice, distance of clitoral hood to labia majora, and length and depth of labia minora. Qualitative descriptors of the clitoral hood and labia were recorded. Patients were grouped into age ranges for analysis: 0-3 years, 4-8 years, 9-12 years, and 13-16 years. RESULTS: Fifty-eight girls were examined. There was a linear relationship between age and genital structure size. In the majority of patients, the labia minora converged under the clitoral glans, separate to the clitoral hood. Four shapes of clitoral hood were observed: horseshoe, trumpet, coffee bean, and tent. DISCUSSION: This study observed great variation in size and morphology of pediatric female genitalia, which is in keeping with other studies. The study was limited by ability to recruit older patients to the study (girls aged 11-16 years) and, therefore, there were lower numbers in this age category. However, the trends that were observed were present in both younger and older girls. CONCLUSION: External genitalia size and morphology are varied in the pediatric female population. The clitoral hood and labia minora were observed to be distinctly separate structures. This study provides a reference for surgeons undertaking genital reconstruction procedures. The study demonstrated that the clitoral hood and labia minora are anatomically distinct structures.

Outcomes following 'mini' percutaneous nephrolithotomy for renal calculi in children. A single-centre study.

INTRODUCTION: This retrospective review was undertaken to identify the postoperative outcomes of children undergoing 'mini' percutaneous nephrolithotomy (MPCNL) at a single institution. OBJECTIVE: Outcomes measured included: percentage of stone clearance, postoperative analgesia requirements, the need for intraoperative or postoperative blood transfusion, length of stay and morbidity. STUDY DESIGN: A total of 46 patients were reviewed over a two-and-a-half-year period; the mean age was 7.3 years (range: 1-16 years). The MPCNL was performed with a radiological-guided peripheral puncture, followed by dilatation of the nephrostomy tract to a maximum Amplatz sheath size of 16-French; an 11-French nephroscope was used. Stone disintegration was achieved either with pneumatic or laser lithotripsy. RESULTS: Complete stone clearance was achieved in 35/46 children (76%). The remaining 11 children had a stone clearance rate of over 80%. No patients required intraoperative/postoperative blood transfusion. A total of 39% of patients were managed on simple/non-opiate based analgesia, with 54% requiring opioid analgesia postoperatively for less than 24 h. There were no procedure-related complications and no mortalities. The mean length of stay was 2.24 days. DISCUSSION: The management of urolithiasis can be challenging in children. The use of percutaneous nephrolithotomy, is becoming increasingly popular in the treatment of paediatric urolithiasis. The stone clearance rate in children undergoing standard PCNL, has been reported to be 50-98% in the literature [1,2,3,4]. Samad et al. [2] in 2006, reported their experience in 188 consecutive PCNLs, using a 17Fr or 26Fr nephroscope. Their largest sub group included children aged >5-16 yrs. Within this group, 57% were treated with a 17Fr nephroscope and 43% with the 26Fr nephroscope, achieving stone clearance of only 47% with PCNL monotherapy. In this group the transfusion rate was 3% [2]. Badawy et al., reported their experience of 60 children in 1999, using a 26 or 28Fr Amplatz sheath. They reported an 83.3% stone clearance with single session PCNL, with only one procedure being abandoned due to intraoperative bleeding requiring blood transfusion [3]. In 2007, Bilen et al. reported their experience and compared the use of 26Fr, 20Fr and 14Fr (mini) PCNL. Stone size, previous surgery and the mean haemoglobin drop postoperatively did not change between the groups, however the blood transfusion rate was higher in the 26Fr and 20Fr Amplatz sheath groups. The stone clearance was highest in the 'mini PCNL' group at 90%, compared to 69.5% in the 26Fr and 80% in the 20Fr group [4]. MPCNL has become increasingly popular over recent years, with stone clearance reported as 80-85% [5-7] following a single session of MPCNL as monotherapy. In 2012, Yan et al. reported 85.2% stone clearance with mini PCNL monotherapy (tract size 14-16Fr), with no children requiring blood transfusion [6]. Zeng et al. reported their experience of 331 renal units in children, with stone clearance rates reaching 80.4% and a blood transfusion rate of 3.1% [8]. In our centre, we do not perform postoperative haemoglobin levels as a matter of routine and any investigations are performed on an intention to treat principle. Bilen et al. reported no blood transfusions being required in their cohort of patients undergoing MPCNL [4] and this is supported by Yan et al. [6]. CONCLUSION: Mini PCNL is an effective and safe procedure for the treatment of paediatric renal stones. In the present series, all children achieved greater than 80% stone clearance, none received a blood transfusion (intra/postoperatively) and there were no mortalities. Postoperative pain was managed with simple analgesia in 39%; however, the majority required opiate analgesia for less than 24 hours.

Trace analysis of lead in blood, aluminium and manganese in serum and chromium in urine by graphite furnace atomic absorption spectrometry.

A graphite furnace atomizer with automatic sampler is used to measure low levels of trace metals in biological samples by atomic absorption spectrometry. With blood and serum, the sample treatment consists of diluting (1:1) with aqueous Triton X-100 solution, centrifuging in the case of blood, and dispensing the liquid directly into a pyrolytic coated graphite tube. Sample volumes for blood and serum range from 5 to 10 microL. Stabilized urine (25 microL) is analyzed directly. The possibility of contamination is minimized by this simple procedure. The methods described minimize sample handling and involve reagents which are virtually free of contamination of the analytes. Background correction is necessary except for the determination of aluminium in serum, and precisions range from 0.7% to 4.3% RSD. The standard additions technique is used to establish the calibration and the required volume of sample and aqueous addition is automatically dispensed directly into the graphite tube.

Recognition of television images as a developmental milestone in young children: observational study.

OBJECTIVES: To determine the age at which children with apparently normal development can recognise the television image of a cat, dog, or baby. DESIGN: Observational study. SETTING: District general hospital in north London. SUBJECTS: 797 children with apparently normal development aged between 8 and 23 months and 26 children with Down's syndrome aged 18 months. OUTCOME MEASURES: Whether or not the child recognised the television image of a cat, dog, or baby by naming, imitating, or pointing at the image. RESULTS: By 18 months of age 96% (95% confidence interval 94% to 98%) of normal children recognised the television image of a cat, dog, or baby compared with 5 of 26 (19%) children with Down's syndrome. CONCLUSION: Recognition of the television image of a cat, dog, or baby is a simple milestone, which may help in the developmental assessment of young children.

Family coping, styles, and challenges.

Creating a therapeutic partnership with patients and families during their crisis with cancer is both a challenging and extremely rewarding experience for the oncology nurse. Each family brings to the experience its own structure, maturational stage, culture, and history. They bring individual and group emotional responses, coping strategies and conflicts when confronting a disease over which they have no control. This article describes the nature of contemporary families within the context of initial and ongoing nursing assessment. It also provides examples of family cancer experiences and the therapeutic approaches selected by nurses faced with the challenges of individual and family coping styles.

Reimbursement warfare: who loses?

The challenge facing healthcare providers is to maximize available reimbursement to cover home care and outpatient management for a growing number of oncology patients who no longer meet inpatient criteria.

Health promotion in primary care: a survey of U.S. family practitioners.

A national sample of family practice physicians reported on the treatments and referrals they provide for each of three behavioral health risks--cigarette smoking, obesity, and insufficient exercise--and on obstacles to effective office-based health promotion. Most respondents reported regular health education and advice, but infrequent systematic treatment or referral for the substantial proportions of their patients who smoke cigarettes (40%), are obese (40%), or get too little exercise (70%). Results confirm past impressions that primary-care physicians (a) are somewhat reluctant to treat such problems, (b) overutilize relatively ineffective risk education strategies, and (c) underutilize potentially more effective behavioral or psychological treatments, either in their practices or via referral to outside programs and specialists. Physicians' pessimism about their patients' abilities to change health lifestyles, a lack of confidence in their own and outside treatments, and perceived patient rejection of referral for lifestyle change treatment, appear the major contributors to this underutilization along with the known financial and organizational obstacles to office-based health promotion and a lack of time and training for these activities. Suggestions for improving primary-care training and supports for health-promotion services are offered.

The indoleamine hypothesis of depression: an overview and pilot study.

This paper reviews the evidence for a specific indoleamine deficiency in depression and the attempts to correct this suspected deficiency with serotonin precursors. It also presents the clinical and biochemical data on six patients with depression treated with L-5-HTP in a nonrandom, double-blind protocol. The oral administration of L5-HTP was associated with a rise in CSF5-HIAA, but only two of six patients studied had any decrease in depression ratings. 5-HTP was also shown to decrease urinary excretion of 17 hydroxycorticosteroids in twodepressed patients and three normal controls suggesting an interrelationship between serotonin metabolism and the pituitary adrenal system. This leads to the suggestion that in a postulated subgroup of depressed patients with pituitary adrenal hyperactivity and evidence of serotonin deficiency, L5-HTP deserves a further trial as an experimental treatment.