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Pharmaceutical Research - One of the major reasons why central nervous system (CNS)-drug development has been challenging in the past, is the barriers that prevent substances entering from the...  相似文献   
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Hypogonadotrophic hypogonadism (HH) is a rare disorder that manifests absent puberty and infertility. Genetic syndromes with hypogonadism, such as Klinefelter syndrome, are associated with an increased risk of neurodevelopmental disorders (NDDs). However, it is not clear whether patients with HH or transient delayed puberty in general, have an increased risk of NDDs. We performed a register‐based study on a national cohort of 264 patients with HH and 7447 patients diagnosed with delayed puberty that was matched with 2640 and 74 470 controls, respectively. The outcome was defined as having any of the following NDD diagnoses: (i) autism spectrum disorder (ASD); (ii) attention deficit hyperactivity disorder (ADHD); or (iii) intellectual disability (ID). Additional sensitivity analyses were performed to control for different parental and birth variables, as well as diagnosed malformation syndromes and chromosomal anomalies (ie, Down’s and Turner syndromes). Patients with HH had increased risk for being diagnosed with ASD (odds ratio [OR] = 5.7; 95% confidence interval [CI] = 2.6‐12.6), ADHD (OR = 3.0; 95% CI = 1.8‐5.1) and ID (OR = 18.0; 95% CI = 8.9‐36.3) compared to controls. Patients with delayed puberty also had a significantly increased risk of being diagnosed with an NDD. These associations remained significant after adjustments. This is the first study to demonstrate a significant association between HH, delayed puberty and NDDs in a population‐based cohort. Clinicians should be aware of the overlap between these disorders. Further studies should explore the mechanisms behind these associations.  相似文献   
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PurposeThe purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa).Methods and MaterialsDuring the years 1999–2008, 241 patients with PCa who underwent LDR-BT with I125 and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed.ResultsAll D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores (p = 0.016) and higher initial urine residual volumes (p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively.ConclusionsThe treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.  相似文献   
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Variations of the nonrecombining Y‐chromosomal region were investigated in 159 unrelated Baltic‐speaking ethnic Latvians from four different geographic regions, using 28 biallelic markers and 12 short tandem repeats. Eleven different haplogroups (hgs) were detected in a regionally homogeneous Latvian population, among which N1c, R1a, and I1 cover more than 85% of its paternal lineages. When compared its closest geographic neighbors, the composition of the Latvian Y‐chromosomal gene pool was found to be very similar to those of Lithuanians and Estonians. Despite the comparable frequency distribution of hg N1c in Latvians and Lithuanians with the Finno‐Ugric‐speaking populations from the Eastern coast of the Baltic Sea, the observed differences in allelic variances of N1c haplotypes between these two groups are in concordance with the previously stated hypothesis of different dispersal ways of this lineage in the region. More than a third of Latvian paternal lineages belong specifically to a recently defined R1a‐M558 hg, indicating an influence from a common source within Eastern Slavic populations on the formation of the present‐day Latvian Y‐chromosome gene pool.  相似文献   
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Mismatch negativity (MMN), an ERP elicited by a deviant stimulus in a train of standard stimuli, has been suggested to be associated to glutamatergic neurotransmission, mediated by glutamatergic NMDA receptors. In this study, we examined the relationship between interindividual variation of 1H‐MRS‐measured glutamate+glutamine (Glx) in the superior temporal gyrus and MMN for duration and frequency deviants in 19 healthy young adults (9 male). We found a significant relationship between the peak latency of the duration‐MMN peak and creatine‐scaled Glx (p = .0003, η2 = .43), with increased Glx level being associated to earlier peak of the duration‐MMN (r = ?.63). In contrast, the amplitude of the duration‐MMN was not related to Glx. There was no significant relationship between Glx and the frequency‐MMN. The present study is the first to demonstrate that interindividual variation in the glutamatergic neurotransmission affects the MMN response in healthy individuals.  相似文献   
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