The Endocannabinoid System: A Putative Role in Neurodegenerative Diseases

BACKGROUND: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. OBJECTIVES: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. MATERIALS AND METHODS: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. RESULTS: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. CONCLUSIONS: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

HiCeekR: A Novel Shiny App for Hi-C Data Analysis

The High-throughput Chromosome Conformation Capture (Hi-C) technique combines the power of the Next Generation Sequencing technologies with chromosome conformation capture approach to study the 3D chromatin organization at the genome-wide scale. Although such a technique is quite recent, many tools are already available for pre-processing and analyzing Hi-C data, allowing to identify chromatin loops, topological associating domains and A/B compartments. However, only a few of them provide an exhaustive analysis pipeline or allow to easily integrate and visualize other omic layers. Moreover, most of the available tools are designed for expert users, who have great confidence with command-line applications. In this paper, we present HiCeekR (https://github.com/lucidif/HiCeekR), a novel R Graphical User Interface (GUI) that allows researchers to easily perform a complete Hi-C data analysis. With the aid of the Shiny libraries, it integrates several R/Bioconductor packages for Hi-C data analysis and visualization, guiding the user during the entire process. Here, we describe its architecture and functionalities, then illustrate its capabilities using a publicly available dataset

HiCeekR: A Novel Shiny App for Hi-C Data Analysis

The High-throughput Chromosome Conformation Capture (Hi-C) technique combines the power of the Next Generation Sequencing technologies with chromosome conformation capture approach to study the 3D chromatin organization at the genome-wide scale. Although such a technique is quite recent, many tools are already available for pre-processing and analyzing Hi-C data, allowing to identify chromatin loops, topological associating domains and A/B compartments. However, only a few of them provide an exhaustive analysis pipeline or allow to easily integrate and visualize other omic layers. Moreover, most of the available tools are designed for expert users, who have great confidence with command-line applications. In this paper, we present HiCeekR (https://github.com/lucidif/HiCeekR), a novel R Graphical User Interface (GUI) that allows researchers to easily perform a complete Hi-C data analysis. With the aid of the Shiny libraries, it integrates several R/Bioconductor packages for Hi-C data analysis and visualization, guiding the user during the entire process. Here, we describe its architecture and functionalities, then illustrate its capabilities using a publicly available dataset

Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose

Abstract OBJECTIVE: To evaluate adult height (AH) in 25 girls with Turner syndrome (TS) who were treated from before 6 years of age for 10.0 \ub1 1.7 years with a fixed GH dose of 0.33 mg/kg per week. PATIENTS AND DESIGN: After a 6-month pretreatment assessment all patients were measured 6-monthly under therapy to assess height SDS (H-SDS) and height velocity (HV) until AH achievement. RESULTS: Following initial acceleration, HV declined after the first 4 years of therapy. At the end of the sixth year of therapy, H-SDS gain was 1.9 \ub1 1.1. Thereafter, H-SDS gain from baseline decreased, becoming 0.9 \ub1 0.9 SDS at AH achievement. Bone maturation velocity did not significantly change throughout the prepubertal period. According to Lyon standards for TS, mean AH SDS was significantly higher than pretreatment H-SDS (P<0.0001), with a mean H-SDS change of 0.9 \ub1 0.9. However, the prevalence of patients with AH <-2 SDS (according to Semp\ue9 standards) was close to those recorded at the start of therapy (16/25 vs 18/25). No significant differences in terms of AH were found between patients with either X monosomy or X-chromosomal abnormalities and between girls with either spontaneous or induced puberty. CONCLUSIONS: We infer that the therapeutic regimen adopted in this prospective study is sufficient to induce a significant growth acceleration during the first year, but the response waned after 6 years of treatment

The Evolution of Thyroid Function after Presenting with Hashimoto Thyroiditis is Different between Initially Euthyroid Girls with and Those without Turner Syndrome

AIM: To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS. DESIGN: In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time. RESULTS: At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype. CONCLUSIONS: An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotyp

The Evolution of Thyroid Function after Presenting with Hashimoto Thyroiditis is Different between Initially Euthyroid Girls with and Those without Turner Syndrome

Aim: To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS. Design: In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time. Results: At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype. Conclusions: An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotype

Levothyroxine Treatment in Pediatric Benign Thyroid Nodules

Aim: To evaluate the effectiveness of levothyroxine therapy in benign thyroid nodules in pediatrics. Methods: Data from 78 euthyroid children and adolescents with benign thyroid nodules were retrospectively collected. Subjects were divided into 2 groups: levothyroxine treated (n = 36) and nontreated (n = 42), and the clinical, laboratory and sonographic features of the 2 groups were compared. Nodules were considered benign according to histology, fine-needle aspiration biopsy or by features suggestive for benignity. The groups were followed up for 2.4 +/- 1.3 years, and treated patients received a mean dose of levothyroxine of 1.69 +/- 0.66 mu g/kg/clay. Results: Patients in the treated and nontreated groups were comparable for age, sex and follow-up. A reduction in nodule diameter from 2.24 +/- 0.94 to 1.86 +/- 1.17 cm (p = 0.039) was observed in treated patients, whereas the nodule diameter increased from 1.66 +/- 0.86 to 1.78 +/- 0.91 cm in nontreated patients (p = 0.024). In the treatment group, 11 patients (30.6%) had a reduction greater than 50% and significantly decreased palpable nodules (p < 0.001). A nonsignificant reduction in reported symptoms was observed, too. The change in nodule size was directly correlated with thyroid-stimulating hormone levels (r = 0.640, p < 0.001) and inversely with levothyroxine dose (r = 0.389, p = 0.009). In nontreated subjects, both palpable nodules and symptoms increased. Conclusion: This study supports levothyroxine treatment effectiveness in shrinking benign nodules. Copyright (C) 2010 S. Karger AG, Base

Serum Thyrotropin Concentration in Children with Isolated Thyroid Nodules

Objective To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. Study design This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. Results Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P 2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology. © 2013 Mosby Inc. All rights reserved

Serum Thyrotropin Concentration in Children with Isolated Thyroid Nodules

Objective To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. Study design This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. Results Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P 2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology. © 2013 Mosby Inc. All rights reserved