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91.
Epidemiological data suggest an association and a common pathogenetic link between male infertility and testicular germ cell tumor (TGCT) development. Genome-wide studies identified that TGCT susceptibility is associated with KITLG (c-KIT ligand), which regulates the formation of primordial germ cells, from which TGCT is believed to arise and spermatogenesis develops. In this study, we analyzed the link between KITLG, TGCT, and spermatogenic disruption by performing an association study between the KITLG markers rs995030 and rs4471514 and 426 TGCT cases and 614 controls with normal and abnormal sperm count. We found that TGCT risk was increased more than twofold per copy of the major G allele and A allele in KITLG rs995030 and rs4471514 (odds ratio (OR)=2.38, 95% confidence interval (95% CI)=1.81-3.12; OR=2.43, 95% CI=1.86-3.17 respectively), and homozygotes for the risk allele had a sevenfold increased risk of TGCT. KITLG markers were strongly associated with seminoma subtype (per allele risk increased more than threefold, homozygote risk increased by 13- to 16-fold) and weakly with nonseminoma. KITLG markers were not associated with sperm production, as no difference was observed in men with normozoospermia and azoo-oligozoospermia, both in controls and in TGCT cases. In conclusion, this study provides evidence that KITLG variants are involved in TGCT development and they represent an independent and strong specific risk factor for TGCT independently from spermatogenic function. A shared genetic cause and a common pathogenetic link between TGCT development and impairment of spermatogenesis are not evident from this study. 相似文献
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Umberto Tarantino Ezio Fanucci Riccardo Iundusi Monica Celi Simone Altobelli Elena Gasbarra Giovanni Simonetti Guglielmo Manenti 《Journal of orthopaedics and traumatology》2013,14(1):15-22
Background
Patients with low back pain frequently demonstrate recumbent magnetic resonance imaging (MRI) alterations not always related to homogeneous clinical symptoms. The purpose of this study was to evaluate and quantify the statistical significance of variations of some anatomical parameters of the lumbosacral spine and reveal occult disc pathologies from recumbent to upright position in patients with acute and chronic low back pain.Materials and methods
Fifty-seven patients complaining of low back pain (27 women, 30 men) underwent dynamic lumbosacral MRI with a 0.25-T tilting system (G-scan Esaote). We settled five parameters for which variations have been evaluated: lumbosacral angle, lordosis angle, L3–L4 intersomatic disc height, L3–L4 interspinous processes distance, and widest anteroposterior dural sac diameter. Images were obtained in both recumbent and upright positions.Results
Statistically significant differences [one-way analysis of variance (ANOVA), p = 0.0043] were found between each pair of values of parameters sampled in recumbent and upright positions. In 70 % of patients, on visual qualitative analysis only, an increment of disc protrusions and/or spondylolisthesis was found in the upright position; in three cases, in the upright position only, an interarticular pseudocyst was found.Conclusions
Dynamic MRI with an open-configuration, low-field tilting MRI system is a feasible and promising tool to study degenerative pathology of the spine. Moreover, in cases of low back pain with negative MRI in the recumbent position or in patients with pain in the upright position only, tilting MRI permits visualization of occult spine and disc pathologies in patients with acute or chronic low back pain. 相似文献95.
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Chiara Terracciano Emanuele Rastelli Maria Morello Monica Celi Elisabetta Bucci Giovanni Antonini Ottavia Porzio Umberto Tarantino Rossella Zenobi Roberto Massa 《Journal of neurology》2013,260(9):2330-2334
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness. 相似文献
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Andrea E. Cavanna Chiara Luoni Claudia Selvini Rosanna Blangiardo Clare M. Eddy Paola R. Silvestri Paola V. Calì Emanuela Gagliardi Umberto Balottin Francesco Cardona Renata Rizzo Cristiano Termine 《Pediatric neurology》2013,48(2):111-114
Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and is often associated with comorbid behavioral problems. Research with generic instruments in child populations showed that comorbid disorders can have a greater impact on health-related quality of life than tic severity. This study investigated the usefulness of a newly developed disease-specific instrument, the Gilles de la Tourette Syndrome–Quality of Life Scale for Children and Adolescents (GTS-QOL-C&A), in assessing health-related quality of life in young patients with Tourette syndrome with and without behavioral comorbidity. We recruited 75 patients with Tourette syndrome (60 males; age 12.4 ± 3.2 years). All participants were evaluated by a neuropsychiatrist and completed a standardized psychometric battery, including the GTS-QOL-C&A, Child Depression Inventory, and Multidimensional Anxiety Scale for Children. Forty-two patients (56%) fulfilled diagnostic criteria for at least one comorbidity: obsessive-compulsive disorder (n = 25 patients [33.3%]); attention deficit/hyperactivity disorder (n = 6 patients [8%]); both (n = 11 patients [14.7%]). The GTS-QOL-C&A demonstrated usefulness in differentiating “pure” Tourette syndrome from Tourette syndrome “plus” behavioral problems with regard to health-related quality of life scores for the obsessive-compulsive subscale. In addition to focusing on core tic symptoms, the GTS-QOL-C&A showed sensitivity to the impact of behavioral comorbidities on health-related quality of life and can usefully complement existing nonspecific instruments. 相似文献
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Patrizia Aracri Alida Amadeo Maria Enrica Pasini Umberto Fascio Andrea Becchetti 《Synapse (New York, N.Y.)》2013,67(6):338-357
We studied how nicotinic acetylcholine receptors (nAChRs) regulate glutamate release in the secondary motor area (Fr2) of the dorsomedial murine prefrontal cortex, in the presence of steady agonist levels. Fr2 mediates response to behavioral situations that require immediate attention and is a candidate for generating seizures in the frontal epilepsies caused by mutant nAChRs. Morphological analysis showed a peculiar chemoarchitecture and laminar distribution of pyramidal cells and interneurons. Tonic application of 5 µM nicotine on Layer V pyramidal neurons strongly increased the frequency of spontaneous glutamatergic excitatory postsynaptic currents. The effect was inhibited by 1 µM dihydro‐β‐erythroidine (which blocks α4‐containing nAChRs) but not by 10 nM methyllicaconitine (which blocks α7‐containing receptors). Excitatory postsynaptic currents s were also stimulated by 5‐iodo‐3‐[2(S)‐azetidinylmethoxy]pyridine, selective for β2‐containing receptors, in a dihydro‐β‐erythroidine ‐sensitive way. We next studied the association of α4 with different populations of glutamatergic terminals, by using as markers the vesicular glutamate transporter type (VGLUT) 1 for corticocortical synapses and VGLUT2 for thalamocortical projecting fibers. Immunoblots showed higher expression of α4 in Fr2, as compared with the somatosensory cortex. Immunofluorescence showed intense VGLUT1 staining throughout the cortical layers, whereas VGLUT2 immunoreactivity displayed a more distinct laminar distribution. In Layer V, colocalization of α4 nAChR subunit with both VGLUT1 and VGLUT2 was considerably stronger in Fr2 than in somatosensory cortex. Thus, in Fr2, α4β2 nAChRs are expressed in both intrinsic and extrinsic glutamatergic terminals and give a major contribution to control glutamate release in Layer V, in the presence of tonic agonist levels. Synapse 00:000–000, 2013 . © 2013 Wiley Periodicals, Inc. 相似文献
100.
Cristina Sánchez‐Castañeda Andrea Cherubini Francesca Elifani Patrice Péran Sara Orobello Giovanni Capelli Umberto Sabatini Ferdinando Squitieri 《Human brain mapping》2013,34(7):1625-1635
Neurodegeneration of the striatum in Huntington disease (HD) is characterized by loss of medium‐spiny neurons, huntingtin nuclear inclusions, reactive gliosis, and iron accumulation. Neuroimaging allows in vivo detection of the macro‐ and micro‐structural changes that occur from presymptomatic stages of the disease (preHD). The aim of our study was to evaluate the reliability of multimodal imaging as an in vivo biomarker of vulnerability and development of the disease and to characterize macro‐ and micro‐structural changes in subcortical nuclei in HD. Macrostructure (T1‐weighted images), microstructure (diffusion tensor imaging), and iron content (R relaxometry) of subcortical nuclei and medial temporal lobe structures were evaluated by a 3 T scanner in 17 preHD carriers, 12 early‐stage patients and 29 matched controls. We observed a volume reduction and microstructural changes in the basal ganglia (caudate, putamen, and globus pallidus) and iron accumulation in the globus pallidus in both preHD and symptomatic subjects; all these features were significantly more pronounced in patients, in whom degeneration extended to the other subcortical nuclei (i.e., thalamus and accumbens). Mean diffusivity (MD) was the most powerful predictor in models explaining more than 50% of the variability in HD development in the caudate, putamen, and thalamus. These findings suggest that the measurement of MD may further enhance the well‐known predictive value of striatal volume to assess disease progression as it is highly sensitive to tissue microimpairment. Multimodal imaging may detect brain changes even in preHD stages. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc. 相似文献