Depression in Diabetic Patients: What Is the Link With Eating Disorders? Results of a Study in a Representative Sample of Patients With Type 1 Diabetes

Comorbidity between diabetes and depression, and diabetes and eating disorders (ED) conveys significant diagnostic, clinical and therapeutic implications. The present study was conducted on a sample of adult outpatients affected by Type 1 Diabetes (T1DM) to assess lifetime prevalence of ED; current prevalence of depression and Disturbed Eating Behaviors (DEB) and their impact on glycemic control. We hypothesized that patients with depression would have higher rates of lifetime ED and current DEB. We hypothesized a significant and independent association between DEB and the prevalence of depression

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Excavating the Roman peasant II: excavations at Case Nuove, Cinigiano (GR)

This report details the survey, excavations and materials analysis carried out at Case Nuove (GR) in Tuscany, a site identified by surface survey as a possible rural house, but which excavation and materials analysis suggest was a small-scale agro-processing point of late Republican date. Through accompanying analysis of pollen and land-use data, the article considers the problems this type of site — the stand-alone agro-processing point — presents for interpretations of the Roman landscape. The survey, excavations and materials analysis of Case Nuove revealed a small- scale agro-processing site, serving perhaps as a collective processing point for local farmers but controlled, at least in part, by a local villa. While only a single site in a complex landscape, it is hoped that the results from Case Nuove illuminate the importance of productive and processing activities as components of Roman landscapes and the embeddedness of such activities in their locale, that is, not only in the plant and physical landscapes, but also in the social complex formed by near (and far) human settlement

Assessment of eating disorders with the diabetes eating problems survey - revised (DEPS-R) in a representative sample of insulin-treated diabetic patients: A validation study in Italy

Background: The purpose of the study was to evaluate in a sample of insulin-treated diabetic patients, with type 1 or type 2 diabetes, the psychometric characteristics of the Italian version of the DEPS-R scale, a diabetes-specific self-report questionnaire used to analyze disordered eating behaviors. Methods: The study was performed on 211 consecutive insulin-treated diabetic patients attending two specialist centers. Lifetime prevalence of eating disorders (EDs) according to DSM-IV and DSM-5 criteria were assessed by means of the Module H of the Structured Clinical Interview for DSM IV Axis I Disorder and the Module H modified, according to DSM-5 criteria. The following questionnaires were administered: DEPS-R and the Eating Disorder Inventory - 3 (EDI-3). Test/retest reproducibility was assessed on a subgroup of 70 patients. The factorial structure, internal consistency, test-retest reliability and concurrent validity of DEPS-R were assessed. Results: Overall, 21.8% of the sample met criteria for at least one DSM-5 diagnosis of ED. A "clinical risk" of ED was observed in 13.3% of the sample. Females displayed higher scores at DEPS-R, a higher percentage of at least one diagnosis of ED and a higher clinical risk for ED. A high level of reproducibility and homogeneity of the scale were revealed. A significant correlation was detected between DEPS-R and the 3 ED risk scales of EDI-3. Conclusions: The data confirmed the overall reliability and validity of the scale. In view of the significance and implications of EDs in diabetic patients, it should be conducted a more extensive investigation of the phenomenon by means of evaluation instruments of demonstrated validity and reliability

CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n= 64) and apparently sporadic ALS (n= 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ~1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs

ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

Abstract Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival

HFE p.H63D polymorphism does not influence ALS phenotype and survival

It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients

ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients

TBK1 is associated with ALS and ALS-FTD in Sardinian patients

Recently, mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina). Genome analysis Toolkit was used to align and to code variants according to Human Genome (UCSC hg19). Mutation was confirmed with Sanger sequence. In our screening of 186 Sardinian ALS cases, we found 3 (1.6%) patients carrying 3 distinct novel genetic variants: a nonsynonymous SNV c.1150C>T leading to a p.Arg384Thr change in exon 9; a nonsynonymous SNV c.1331G>A causes a p.Arg444Gln change in exon 11; and a frameshift deletion c.2070delG (p.Met690fs) at the exon 20 of the gene leading to a stop at 693 codon. The latter patients also carried missense mutation c.98C>T of the SQSTM1 gene causing a substitution of an arginine with a valine at the position 33 (p.Arg33Val). All variants were found to be deleterious according to in silico predictions. All cases were apparently sporadic and one of them showed frontotemporal dementia associated to ALS. These mutations were not found in 2 cohorts of 6780 ethnic-matched controls. We have found that TBK1 mutations account for 1.6% of Sardinian ALS cases. Our data support the notion that TBK1 is a novel ALS gene, providing important evidence complementary to the first descriptions