Brain source-connectivity analysis was done GI symptoms were ass

Brain source-connectivity analysis was done. GI symptoms were assessed with the gastroparesis cardinal symptom index and quality of life (QOL) with SF-36. Any changes in brain source connectivity were correlated to duration of the disease, heart beat-to-beat intervals (RRs), clinical symptoms, and QOL of the patients.

Results: Diabetic patients with GI symptoms showed changes relative to controls in the operculum-cingulate network with the operculum source localized deeper and more

anterior (P <= 0.001) and the cingulate source localized more anterior (P = 0.03). The shift of operculum source was correlated with the duration of the disease, severity of GI symptoms, and decreased RR (P < 0.05). The shift of the cingulate source was correlated learn more with the mental QOL (P = 0.04). In healthy controls, the contribution of the cingulate source to the network was higher than the contribution of the operculum source (P <= 0.001), whereas in patients the contribution of the two sources was comparable.

Conclusion: This study gives further evidence for CNS involvement in diabetes. Since network

reorganizations were correlated to GI symptoms, irregularities of rectal-evoked potentials can be viewed as a proxy for abnormal bottom-up visceral afferent processing. The network changes might serve as a biomarker for disturbed sensory visceral processing of VX-661 cost GI symptoms in diabetes patients. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We found the main effects of harm avoidance temperament in predicting bipolar I and II, but the interaction between novelty seeking and Ser9Gly polymorphisms of dopamine D3 receptor gene was demonstrated in bipolar-I patients only. This study provided evidence that differences existed between BP-I and

BPII in gene and temperament interactions. (C) 2010 Elsevier Ireland Ltd. All click here rights reserved.”
“A polyomavirus was isolated from the eyes of horses, and the sequence was determined. A nearly identical VP1 sequence was amplified from the kidney of another animal. We report the complete genome sequence of the first polyomavirus to be isolated from a horse. Analysis shows it to be most closely related overall to human and nonhuman primate polyomaviruses.”
“Growing evidence has suggested that hydrogen sulfide (H2S) acts as a novel neuro-modulator and neuroprotective agent; however, it remains to be investigated whether H2S has a direct effect on neural stem cells (NSCs). We report here that NSCs expressed cystathionine p synthase (CBS) and addition of exogenous H2S donor, L-cysteine, stimulated proliferation and increased the differentiation potential of NSCs to neurons and astroglia.

Candidate-gene based population and family association studies ha

Candidate-gene based population and family association studies have implicated some ionotrophic glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic

glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further replication studies are needed to validate these results. There is at present no consensus on specific single nucleotide polymorphisms or halpotypes associated with the particular candidate gene loci in these EPZ004777 concentration illnesses. The genetic architecture of glutamate systems in bipolar disorder need to be better studied in view of recent data suggesting an overlap in the genetic aetiology of SZ and BD. There is a pressing need to integrate research platforms in genomics, epistatic models, proteomics, metabolomics, neuroimaging technology and translational studies in order to allow a more integrated understanding of glutamate and GABAergic signalling processes and aberrations in CBL0137 SZ and BD as well as their relationships with clinical presentations and treatment progress over time. (C) 2010 Elsevier

Ltd. All rights reserved.”
“Although both obesity and the metabolic syndrome (MetS) are known risk factors for decline in physical function, the joint association of obesity and metabolic alterations with risk of incident mobility limitation is unknown.

Data are from 2,984 women and men aged 70-79 years participating in the Health, Aging, and Body Composition Study

without mobility limitation at baseline. Obesity was defined as body mass index greater than or equal Selleckchem GKT137831 to 30 kg/m(2) and the MetS as meeting greater than or equal to 3 of the ATP III criteria. Mobility limitation was defined as any difficulty walking one-quarter mile or climbing 10 steps during two consecutive semiannual assessments for more than 6.5 years.

Incidence of mobility limitation was 55% in women and 44% in men. In women, adjusted risk of developing mobility limitation was progressively greater in nonobese participants with the MetS (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.24-1.80), obese participants without the MetS (HR = 1.95, 95% CI = 1.51-2.53), and obese participants with the MetS (HR = 2.16, 95% CI = 1.78-2.63) relative to the nonobese without the MetS. In men, the corresponding adjusted HRs (95% CI) were 1.07 (0.87-1.32), 1.64 (1.19-2.25), and 1.41 (1.12-1.78). Elevated inflammatory markers partly explained the association between obesity, the MetS, and mobility limitation, particularly in nonobese and obese participants with the MetS.

Obesity itself, independent of its metabolic consequences, is a risk factor for mobility limitation among obese older adults. In addition, having the MetS increases the risk of functional decline in older nonobese women but not in men.

However, here we show that staurosporine does not affect PDK1 pho

However, here we show that staurosporine does not affect PDK1 phosphorylation of the endogenous PKM zeta in hippocampal slices. Thus, the biochemical in vitro effects of PKM zeta inhibitors correspond with their intracellular effects, and ZIP and chelerythrine, together with scrambled ZIP and staurosporine as controls, are effective tools to examine the function of PKM zeta in neurons.

This article is part of a Special Issue entitled ‘Cognitive Enhancers’. check details (C) 2012 Elsevier Ltd. All rights reserved.”
“Various experimental manipulations, usually

involving drug administration, have been used to produce symptoms of psychosis in healthy volunteers. Different drugs produce both common and distinct symptoms. A challenge is to understand how apparently different

manipulations can produce overlapping symptoms. We suggest that current Bayesian formulations of information processing in the brain provide a framework that maps onto neural circuitry and gives us a context within which we can relate the symptoms of psychosis to their underlying selleck chemicals causes. This helps us to understand the similarities and differences across the common models of psychosis.

The Bayesian approach emphasises processing of information in terms of both prior expectancies and current inputs. A mismatch between these leads us to update inferences about the world and to generate new predictions for the future. According to this model, what we experience shapes what we learn, and what we learn modifies how we experience things.

This simple idea gives us a powerful and flexible way of understanding the symptoms of psychosis where perception, learning and inference are deranged. We examine the predictions of the cognitive model in light of what we understand about the neuropharmacology of psychotomimetic drugs and thereby attempt to account for the common and the distinctive effects of NMDA receptor this website antagonists, serotonergic hallucinogens,

cannabinoids and dopamine agonists.

By acknowledging the importance of perception and perceptual aberration in mediating the positive symptoms of psychosis, the model also provides a useful setting in which to consider an under-researched model of psychosis-sensory deprivation.”
“Positive allosteric modulators of alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket.

Materials and Methods: A retrospective chart review was performed

Materials and Methods: A retrospective chart review was performed of children undergoing hydrocele repair at our institution between 1998 and 2006. Operative Nec-1s cell line reports were reviewed by 2 investigators and intraoperative findings were recorded for statistical analysis relating age and findings at the time of the procedure using logistic regression and ROC analysis. Laterality and recurrence rates were also noted.

Results: In this retrospective chart review 82.1% of hydroceles in children older than 10 years had intraoperative findings

consistent with noncommunicating hydrocele and 86.4% in children older than 12 years were noncommunicating. One hydrocele in the age group older than 12 years was communicating and the history was suggestive of communication. Age was significantly associated

with a patent processus vaginalis (OR 0.783, p <0.0001).

Conclusions: It is possible in children older than 12 years to repair hydroceles through a scrotal incision unless the clinical history is suggestive of Y-27632 order a communication. Children younger than 12 years should undergo inguinal exploration for hydrocele repair.”
“Experiences of odours at meals are thought to affect food preference in many animals. To study appetite modulation by odours, we established a new experimental system based on the modification of a previous method, where flies fed sucrose flavoured with D-limonene subsequently showed reduced appetite to plain sucrose. In this new experimental system, a fly population was divided into two groups: (1) the “”simultaneous”" group of flies was exposed

to D-limonene BV-6 order and sucrose simultaneously for 10 min, and (2) the “”separate”" group of flies was exposed to sucrose alone for 10 min, and 1 h later, to limonene for 10 min. The appetite of flies in the “”separate”" group for sucrose was unaffected by the experiment, but the appetite of flies in the “”simultaneous”" group was significantly decreased, and this effect lasted for >= 3 days. To investigate if this appetite modulation by D-limonene was based on long-term memory formation (protein synthesis), we examined the effects of the protein synthesis inhibitor, cycloheximide. Injection of cycloheximide 1 h after exposure to limonene and sucrose inhibited the appetite suppression in the “”simultaneous”" group of flies. In addition, to exclude the possibility that D-limonene exerted its effect through taste, rather than odour, we examined the effect of removing of the olfactory organs, antennae and maxillary palps on appetite modulation by D-limonene. When the olfactory organs were removed, no reduction in appetite was observed in the flies in the “”simultaneous”" group, indicating olfaction. In our new and effective appetite-modulation system for flies, modulation of appetite by olfactory detection of D-limonene was shown. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

This indicates that the matching algorithm has the potential to b

This indicates that the matching algorithm has the potential to be used for designing industrial enzymes for desired reactions.”
“Immunotherapeutic herpes simplex virus

2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein Givinostat concentration D2 (gD2 Delta TMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4(383-766)), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM2). In addition to eliciting Nec-1s supplier humoral immune responses,

CD4(+) and CD8(+) T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003-or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to

chronic antiviral drugs in the treatment and control of genital herpes disease.”
“Most GDC-0994 scoring functions for protein-protein docking algorithms are either atom-based or residue-based, with the former being able to produce higher quality structures and latter more tolerant to conformational changes upon binding. Earlier, we developed the ZRANK algorithm for reranking docking predictions, with a scoring function that contained only atom-based terms. Here we combine ZRANK’s atom-based potentials with five residue-based potentials published by other labs, as well as an atom-based potential IFACE that we published after ZRANK. We simultaneously optimized the weights for selected combinations of terms in the scoring function, using decoys generated with the protein-protein docking algorithm ZDOCK. We performed rigorous cross validation of the combinations using 96 test cases from a docking benchmark.

Predictors investigated were: symptoms of depression, anxiety, ap

Predictors investigated were: symptoms of depression, anxiety, apathy and sleeping problems.

Results. Affective symptoms were

present in 50-70% of the subjects. The average follow-up period was 5.4 years and 79 subjects (29%) developed AD. Sleeping problems were associated with a decreased risk for AD [odds ratio (OR) 0.35, p<0.001]. Symptoms of depression (OR 0.61, p = 0.059) and anxiety (OR 0.58, p = 0.051) showed a trend in the same direction. The OR of apathy for AD was 0.67 (p = 0.14). Depression was associated with a decreased risk for AD only in subjects without amnestic MCI, but not in subjects with amnestic MCI. Moreover, anxiety was related to the risk for AD differently between learn more subjects diagnosed with AD at the 5-year follow-up (OR 0.23) and

subjects diagnosed with AD at the 10-year follow-up (OR 1.7).

Conclusions. Affective symptoms are associated with a decreased risk for AD. The risk may be dependent on MCI subtype or length of follow-up, but it does not depend on age.”
“The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. Molecular evolutionary analyses YM155 mouse of the 2009 pandemic influenza A H1N1 [A(H1N1)pdm09] virus revealed two major clusters, cluster I and cluster II. Although the pathogenicity of viruses belonging to cluster I, which became extinct by the end of 2009, has been examined in a nonhuman primate model, the pathogenic potential of viruses belonging to cluster II, which has spread more Selleck Alisertib widely in the world, has not been studied in this animal model. Here, we characterized two Norwegian isolates belonging to cluster II, namely, A/Norway/3568/2009 (Norway3568) and A/Norway/3487-2/2009 (Norway3487), which caused distinct clinical symptoms, despite their genetic similarity. We observed more efficient replication in cultured cells and delayed virus clearance from ferret respiratory organs for Norway3487 virus, which was isolated from a severe case, compared with the efficiency of replication and time of clearance of Norway3568 virus, which was isolated from a mild

case. Moreover, Norway3487 virus to some extent caused more severe lung damage in nonhuman primates than did Norway3568 virus. Our data suggest that the distinct replicative and pathogenic potentials of these two viruses may result from differences in their biological properties (e.g., the receptor-binding specificity of hemagglutinin and viral polymerase activity).”
“BACKGROUND: The management of basilar invagination (BI) and atlantoaxial dislocation (AAD) is a challenge.

OBJECTIVE: To describe a new innovative method to reduce BI and AAD through a single-stage posterior approach.

METHODS: Thirty-five patients had irreducible BI and AAD (May 2010 to April 2012). In all patients, reduction of AAD and BI was achieved by using an innovative method of distraction and spacer placement, followed by compression and extension.


“Fragile X Syndrome (FXS) is the most common single-gene i


“Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism.

People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder. Several C188-9 supplier of these aberrant behaviors and FXS-associated synaptic irregularities also occur in “”fragile X mental retardation gene”" knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines – postsynaptic sites for excitatory synapses – in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4- and 8-week-long treatments

significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral selleck compound improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: Dynamic near infrared fluorescence imaging of the urinary tract provides a promising way to diagnose ureteropelvic junction obstruction. Initial studies demonstrated the ability to visualize urine flow and peristalsis in great detail. We analyzed the efficacy of near infrared imaging in evaluating ureteropelvic junction obstruction,

renal involvement and the anatomical detail provided Calpain compared to conventional imaging modalities.

Materials and Methods: Ten swine underwent partial or complete unilateral ureteral obstruction. Groups were survived for the short or the long term. Imaging was performed with mercaptoacetyltriglycine diuretic renogram, magnetic resonance urogram, excretory urogram, ultrasound and near infrared imaging. Scoring systems for ureteropelvic junction obstruction were developed for magnetic resonance urogram and near infrared imaging. Physicians and medical students graded ureteropelvic junction obstruction based on magnetic resonance urogram and near infrared imaging results.

Results: Markers of vascular and urinary dynamics were quantitatively consistent among control renal units.

Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-f

Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-free chow containing 0, 5, 100, or 500 ppm genistein (approximate to 0.0, 0.4, 8.0, and 40.0 mg/kg/day) or 0, 25, 200, or 750 ppm nonylphenol (approximate to 0.0, 2.0,16.0, and 60.0 mg/kg/day). Rats were mated within treatment groups and offspring (F1) maintained on the same diets. Mating for the F1, F2, and F3 (genistein only) was within treatment groups. At postnatal Tozasertib solubility dmso day (PND) 21, the F3 generation began to consume unadulterated phytoestrogen-free chow such that genistein exposure occurred only in utero and preweaning. The F4 generation was never directly exposed to genistein. On PNDs 65-68, intake of regular water and a 3.0% sodium chloride

solution was measured for F1-F4 generations (genistein portion) or F1-F2 (nonylphenol portion). Although body weights were decreased by the highest dietary concentrations of genistein and nonylphenol, there were only minimal effects of exposure

on sodium solution intake. As expected, intake was highest in female rats. With previous data, these results indicate that the dietary concentrations necessary to increase adult sodium solution intake in rats are greater than 500 ppm genistein and 750 ppm nonylphenol and such effects do not appear to increase across generations. Published by Elsevier Inc.”
“Purpose: Navigation for current robotic assisted surgical techniques is primarily accomplished through a stereo pair of laparoscopic camera images. These images provide standard optical visualization PLX4032 mouse of the surface but provide no subsurface information. Image

guidance methods allow the visualization of subsurface information to determine the current position in relationship to that of tracked tools.

Materials and Methods: A robotic image guided surgical system was designed and implemented based on our previous laboratory studies. A series of experiments using tissue mimicking phantoms with injected target lesions was performed. The surgeon was asked to resect “”tumor”" tissue with and without the augmentation of click here image guidance using the da Vinci (R) robotic surgical system. Resections were performed and compared to an ideal resection based on the radius of the tumor measured from preoperative computerized tomography. A quantity called the resection ratio, that is the ratio of resected tissue compared to the ideal resection, was calculated for each of 13 trials and compared.

Results: The mean +/- SD resection ratio of procedures augmented with image guidance was smaller than that of procedures without image guidance (3.26 +/- 1.38 vs 9.01 +/- 1.81, p < 0.01). Additionally, procedures using image guidance were shorter (average 8 vs 13 minutes).

Conclusions: It was demonstrated that there is a benefit from the augmentation of laparoscopic video with updated preoperative images. Incorporating our image guided system into the da Vinci robotic system improved overall tissue resection, as measured by our metric.

Variation in responses to static pain sensitivity was not associa

Variation in responses to static pain sensitivity was not associated with pain intensity

from DOMS while, in contrast, variation in dynamic pain sensitivity was positively associated with variation in pain intensity from DOMS. This finding supports the use of TSS as a marker of the central pain state and potentially as an appropriate measure for treatment monitoring. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: www.selleckchem.com/products/Adrucil(Fluorouracil).html We clarified correlations between symptoms of attention deficit disorder with hyperactivity and voiding dysfunction in children.

Materials and Methods: The study sample consisted of 92 boys and 38 girls 4 to 14 years old who presented at pediatric urology clinics with untreated lower urinary tract symptoms. Parents completed the Swanson, Nolan and Pelham-IV scale. Each subject with a combined score in the first 2 subscales (inattention, hyperactivity/impulsivity) at or above the 90th percentile was classified as having symptoms of attention deficit disorder with hyperactivity. AZD9291 mouse All other cases were classified as non-attention deficit disorder. Voiding dysfunction symptoms were assessed by the Dysfunctional Voiding Symptom Scale. Sleep quality was assessed by the Pediatric

Sleep Questionnaire. We then analyzed correlations between Dysfunctional Voiding Symptom Scale and symptoms of attention deficit disorder with hyperactivity.

Results: The group with symptoms of attention deficit disorder with

hyperactivity had significantly higher scores on the Dysfunctional Voiding Symptom Scale overall and in the “”cannot wait”" subscale compared to the group without attention deficit disorder, as well as poorer sleep quality and lower voiding Givinostat volumes. Overall Dysfunctional Voiding Symptom Scale scores were significantly correlated with overall Swanson, Nolan and Pelham-IV scale scores and also significantly correlated with each of the 3 Swanson, Nolan and Pelham-IV subscales (inattention, hyperactivity/impulsivity and oppositional defiant). Overall Dysfunctional Voiding Symptom Scale scores and scores on the “”cannot wait”" and “”hurt when pee”" subscales were significantly higher for males than for females.

Conclusions: Boys with higher scores of attention deficit disorder with hyperactivity symptoms tend to have higher Dysfunctional Voiding Symptom Scale scores. Lower urinary tract symptoms were significantly correlated with overall Swanson, Nolan and Pelham-IV scores and significantly correlated with each of the 3 subscales. Evaluation of concomitant symptoms of attention deficit disorder with hyperactivity in children with lower urinary tract symptoms is an important clinical concern.”
“The effects of feeding n-6 and n-3 fatty acids to broiler hens on cardiac ventricle fatty acid composition, and prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) production of hatched chicks were investigated.

Conclusions: Masculinization of the alpha ERKO clitoris suggests

Conclusions: Masculinization of the alpha ERKO clitoris suggests a role for estrogen in the development of female external genitalia.

We propose that normal external Avapritinib ic50 genital development requires androgen and estrogen action.”
“The pathways by which painful stimuli are signaled within the human medial temporal lobe are unknown. Rodent studies have shown that nociceptive inputs are transmitted from the brainstem or thalamus through one of two pathways to the central nucleus of the amygdala. The indirect pathway projects from the basal and lateral nuclei of the amygdala to the central nucleus, while the direct pathway projects directly to the central nucleus. We now test the hypothesis that the human ventral amygdala (putative selleck inhibitor basal and lateral nuclei) exerts a causal influence upon the dorsal amygdala (putative central nucleus), during the application of a painful laser stimulus. Local field potentials (LFPs) were recorded from depth electrode contacts implanted in the medial temporal lobe for the treatment of epilepsy, and causal influences were analyzed by Granger causality (GRC). This analysis indicates that the dorsal amygdala exerts a pre-stimulus causal influence upon the hippocampus, consistent with an attention-related response

to the painful laser. Within the amygdala, the analysis indicates that the ventral contacts exert a causal influence upon dorsal contacts, consistent with the human (putative) this website indirect pathway. Potentials evoked by the laser (LEPs) were not recorded in the ventral nuclei, but were recorded at dorsal amygdala contacts which were not preferentially those receiving causal influences from the ventral contacts. Therefore, it seems likely that the putative indirect pathway is associated with causal influences from the ventral to the dorsal amygdala, and is distinct from

the human (putative) indirect pathway which mediates LEPs in the dorsal amygdala. (c) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose: Reports of pubertal hormonal and gonadal status in patients with hypospadias are scarce. We evaluated the pituitary-gonadal axis and gonadal growth in patients with hypospadias at puberty.

Materials and Methods: We retrospectively reviewed serum luteinizing hormone, follicle-stimulating hormone, testosterone and testicular volume at puberty (age 15 years or greater) in the medical charts of patients with hypospadias treated since 1986 and followed at our institution.

Results: Enrolled in this study were 43 patients with a mean age at evaluation of 17.6 years (range 15.1 to 22.8). Of these patients 14 and 29 were treated for mild and severe hypospadias, respectively. Six patients with severe hypospadias underwent bilateral orchiopexy for bilateral undescended testes. All patients were Tanner stage 4 to 5 at evaluation.