Mapping default mode connectivity alterations following a single season of subconcussive impact exposure in youth football

Repetitive head impact (RHI) exposure in collision sports may contribute to adverse neurological outcomes in former players. In contrast to a concussion, or mild traumatic brain injury, “subconcussive” RHIs represent a more frequent and asymptomatic form of exposure. The neural network‐level signatures characterizing subconcussive RHIs in youth collision‐sport cohorts such as American Football are not known. Here, we used resting‐state functional MRI to examine default mode network (DMN) functional connectivity (FC) following a single football season in youth players (n = 50, ages 8–14) without concussion. Football players demonstrated reduced FC across widespread DMN regions compared with non‐collision sport controls at postseason but not preseason. In a subsample from the original cohort (n = 17), players revealed a negative change in FC between preseason and postseason and a positive and compensatory change in FC during the offseason across the majority of DMN regions. Lastly, significant FC changes, including between preseason and postseason and between in‐ and off‐season, were specific to players at the upper end of the head impact frequency distribution. These findings represent initial evidence of network‐level FC abnormalities following repetitive, non‐concussive RHIs in youth football. Furthermore, the number of subconcussive RHIs proved to be a key factor influencing DMN FC.     

Premature pubarche: etiological heterogeneity.

Premature pubarche is characterized by pubic hair, adult type body odor, acne, and axillary hair before 8 yr of age in girls and 9.5 yr of age in boys. Causes of this premature virilization include premature adrenarche, mild errors of steroidogenesis, precocious puberty, and adrenal and gonadal tumors. To determine whether any clinical parameters are helpful in distinguishing which children should undergo further evaluation for mild congenital adrenal hyperplasia, we performed ACTH stimulation tests in 69 children with premature pubarche and 8 pubertal controls. Patients were categorized as having typical (pubic hair with or without axillary hair and body odor) or atypical (pubic hair and genital enlargement) premature pubarche. Blood samples, before and 30 min after iv bolus administration of synthetic ACTH, were obtained for progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, 11-deoxycortisol, and cortisol measurements. The patients were divided into 4 groups based on their individual responses to ACTH stimulation: premature adrenarche (no apparent defect in steroidogenesis), possible decreased 21-hydroxylase activity, possible decreased 3 beta-hydroxysteroid dehydrogenase activity, and indeterminate responses. Five of 11 (45%) children with atypical premature pubarche and 7 of 58 (12%) children with typical premature pubarche were found to have evidence of mild defects in steroidogenesis. Similar to previous reports in postpubertal women, only responses to ACTH stimulation allowed accurate classification of these patients.     

Chronic colitis is associated with a reduction of mucosal alkaline sphingomyelinase activity

BACKGROUND AND AIMS: The hydrolysis of sphingomyelin (SM) generates key molecules regulating cell growth. Animal cancer studies support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. The activity of a specific intestinal alkaline sphingomyelinase (SMase), which hydrolyzes SM, is reduced in colorectal tumors. In this study we measured alkaline SMase activity in patients with longstanding colitis and assessed if a reduction can be used as a marker in surveillance of high risk patients. METHODS: Alkaline SMase activity was measured in 139 colonic biopsies from 34 patients with longstanding, extensive colitis and from 11 controls. Fifteen patients had earlier diagnosis of dysplasia or DNA aneuploidy. Alkaline SMase activity was related to histologic dysplasia and DNA aneuploidy assessed by flow cytometry, patient age, and duration of disease. RESULTS: Alkaline SMase activity was significantly lower in the patient group with and without dysplasia compared with controls (p = 0.006). In biopsies, an association was not found between alkaline SMase activity, dysplasia, or DNA ploidy. However, alkaline SMase activity decreased with age both in patients and controls (p = 0.008). CONCLUSIONS: Reduction of alkaline SMase activity seen in colorectal cancer and adenomas is also present in patients with chronic colitis. It is not complementary to dysplasia or DNA-aneuploidy in the identification of high risk patients. The age-associated decrease of alkaline SMase activity seems to be a general phenomenon indicating premature senescence of the mucosa in longstanding colitis.     

Estrogen Induces Neuropeptide Y (NPY) Y1 receptor gene expression and responsiveness to NPY in gonadotrope-enriched pituitary cell cultures

We showed previously that neuropeptide Y1 receptor (Y1R) expression is increased in the hypothalamus on proestrus afternoon and that this up-regulation of Y1R mRNA may permit neuropeptide Y (NPY) to facilitate release of the preovulatory GnRH surge. Because NPY also modulates LH release directly, we examined steroid regulation of Y1R expression in the female rat anterior pituitary. Treatment of female rats with estrogen in vivo decreased the levels of Y1R mRNA in the whole pituitary gland. In lactotrope/somatotrope-enriched pituitary cells separated by unit gravity sedimentation, 17beta-estradiol (E(2)) treatment likewise suppressed Y1R expression. In contrast, E(2) elevated Y1R mRNA in gonadotrope-enriched cell populations, indicating that estrogen regulates Y1R mRNA expression differently in gonadotropes vs. other pituitary cell types. After exposure to E(2), NPY augmented GnRH-induced LH release from gonadotrope-enriched cells in a manner requiring Y1R activation. Without steroid exposure, this augmentation disappeared, and with progesterone alone, NPY reduced GnRH-induced LH release. In addition, NPY inhibited prolactin secretion from primary pituitary cells in a steroid-free environment, but not in the presence of estrogen. These findings demonstrate that E(2) can directly up-regulate gonadotrope responsiveness to NPY and suggest that this action is mediated at least in part by E(2)'s ability to stimulate Y1R gene expression in gonadotropes. Our observations are consistent with the idea that this regulatory mechanism represents a component of E(2)'s positive feedback actions in pituitary gonadotropes. The biological importance of E(2)'s opposite effects on Y1R expression in other pituitary cell types remains to be determined.     

Laterally spreading tumors--experience based on 138 consecutive cases

BACKGROUND/AIMS: Laterally spreading tumors (LST) are flat elevated neoplastic lesions with diameters equal to or greater than 10 mm. The treatment results of 138 lesions in 131 patients are presented here as a part of a retrospective analysis. METHODOLOGY: Two gastroenterology centers participated in the study in the period from 1/2002-12/2006. During colonoscopy, each superficial lesion was classified according to the Paris endoscopic classification. Endoscopic mucosal resection (EMR) lift and cut was employed. Treatment was considered successful when both endoscopic and histo-pathological criteria of complete resection were fulfilled. RESULTS: A total of 138 LST in 131 patients were diagnosed. Average LST diameter was 25 mm. A total of 5 (3.6%) lesions in 4 patients were referred for primary surgery. One patient was treated with argon plasma coagulation only. EMR was attempted for 132/138 (95.7%) of all LST and was successful in 125 (90.6%) cases. Complications occured in 16/132 (12.1%) patients. Severe complications, defined as decession, emergency surgery, emergency endoscopy and transfusion of eryhrocyte concentrate occured in 5/132 (3.8%). One (0.7%) 69 year-old-male patient died on the third day following EMR due to complications of acute myocardial infarction. CONCLUSION: LST lesions could be efficiently treated with EMR lift and cut method with a reasonable rate of complications.     

Coronary and left ventricular pacing as standby in invasive cardiology.

Coronary pacing using as unipolar negative electrode a guidewire placed in a coronary branch was tested in 349 sites of 300 consecutive patients undergoing coronary angioplasty. It was possible for 339 sites (97%). The threshold currents ranged from 1 to 15 (mean +/- standard deviation 3.4 +/- 2.4) mA. Side effects were seen in 13 patients (4%): 6 (2%) had transient coronary spasm, 4 (1%) had diaphragmatic stimulation, and 3 (1%) had stinging pain at the skin electrode. Of the 10 cases with pacing failure, left ventricular pacing was successfully tested in 5 by introducing the coronary wire or another wire into the left ventricle. It yielded a threshold of 2-8 (3.2 +/- 2.7) mA. Therapeutic pacing for significant bradycardia was required in 7 patients (2%). It was successful in all. Coronary or left ventricular pacing appears to be a simple and reliable temporary measure. When there is no wire in the coronary artery or for diagnostic catheterization, left ventricular pacing can be done using the same setup and any type of guidewire.