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Previous research has documented that patients referred for problems related to alcohol use rely primary on maladaptive coping and are deficient in adaptive coping skills. However, the relation between dispositional and situational coping in these patients is not yet fully understood. Therefore, the first aim of the present study was to assess dispositional and situational coping among individuals with alcohol use disorder compared to matched healthy controls. Furthermore, we aimed at assessing gender differences in dispositional and situational coping among individuals with alcohol use disorder. Fifty-five patients with alcohol use disorder were compared to 55 age, years of education, and gender-matched healthy volunteers. Participants filled out the Coping Orientation to Problem Experiences-New Italian version assessing dispositional coping and the Coping Responses Inventory - Adult Form assessing situational coping. Regarding dispositional coping, patients with alcohol use disorder employed more avoidant coping styles compared to matched healthy controls. No differences between groups emerged on situational coping. With respect to gender differences in dispositional coping, women, regardless of group membership, employed more coping styles aimed at construing a stressful transaction in positive terms and turned to religion more relative to men. With respect to situational coping, women, again regardless of group membership, employed more strategies aimed at construing a stressful transaction in positive terms and more problem-solving strategies compared to men. Results of the present study may assist with treatment planning for alcohol use disorder and lead to the development of treatment programs targeting patients' specific coping difficulties.

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

A. Palotie on työryhmän jäsen. Objective The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p. T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10(-4); OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Graves’ disease (GD) is an autoimmune oligogenic disorder with a strong hereditary component. Several GD susceptibility genes have been identified and confirmed during the last two decades. However, there are very few studies that evaluated susceptibility genes for GD in specific geographic subsets. Previously, we mapped a new locus on chromosome 3q that was unique to GD families of Italian origin. In the present study, we used association analysis of single-nucleotide polymorphism (SNPs) at the 3q locus in a cohort of GD patients of Italian origin in order to prioritize the best candidates among the known genes in this locus to choose the one(s) best supported by the association. DNA samples were genotyped using the Illumina GoldenGate genotyping assay analyzing 690 SNP in the linked 3q locus covering all 124 linkage disequilibrium blocks in this locus. Candidate non-HLA (human-leukocyte-antigen) genes previously reported to be associated with GD and/or other autoimmune disorders were analyzed separately. Three SNPs in the 3q locus showed a nominal association (p

Takayasu's arteritis (TAK) is a rare, chronic large-vessel vasculitis (LVV) that predominantly affects the aorta, its major branches, and the pulmonary arteries. Recent advances in the diagnosis, clinical course, disease assessment with biomarkers/imaging and new clinical tools, patient-reported outcomes, and new treatment options of TAK are discussed in this review. Conventional angiography, the gold standard method for initial diagnosis, appears to have been replaced with new imaging modalities such as magnetic resonance angiography (MRA) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in recent years. MRA and FDG-PET are also promising for the assessment of disease activity. New tools for disease assessment such as Indian Takayasu's Arteritis Score 2010 (ITAS2010) and color Doppler ultrasound (CDUS) aim to better characterize and quantify disease activity however, different imaging modalities in routine follow-up are not incorporated sufficiently in these approaches. Prognosis is possibly getting better, with lower mortality in recent years however, it is difficult to assess the widely different vascular intervention rates among the clinical series. Leflunomide, tumor necrosis factor (TNF)-alpha antagonists, and tocilizumab are new options for patients resistant to conventional therapies. There is a clear need to develop a validated set of outcome measures for use in clinical trials of TAK. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group has taken on this task, finished a Delphi exercise with experts, and aims to develop a core set of outcomes for LVV in accordance with OMERACT Filter 2.0.

Objective and Design to assess if deletion of the angiotensin-converting enzyme (ACE) gene is a risk factor for abdominal aortic aneurysms (AAAs) in normotensive patients. Materials and Methods ACE gene polymorphism was examined by polymerase chain reaction in 124 subjects with AAA and in 112 control subjects. AAA normotensive patients (group A,n=56) were compared to normotensive control subjects (group B, n =112) and to AAA hypertensive patients (group C, n =68). All subjects enrolled in this study were Caucasian and from central and southern Italy.Results the distribution of ACE genotypes was: normotensive patients with AAAs (group A): 3 II, 14 ID, 39 DD; normotensive control subjects (group B): 36 II, 48 ID, 28 DD; hypertensive patients with AAAs (group C): 14 II, 32 ID, 22 DD. The DD genotype was more common in group A than in control groups (A vs B p

BACKGROUND: Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. METHODS: An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction. RESULTS: This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. CONCLUSION: This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases. Background: Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes.Methods: An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction.Results: This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function.Conclusion: This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

Pompe disease is a recessively inherited and often fatal disorder caused by the deficiency of acid α-glucosidase, an enzyme encoded by the GAA gene and needed to break down glycogen in lysosomes. This glycogen storage disease type II has been reported also in Swedish Lapphund dogs. Here we describe the genetic defect in canine Pompe disease and show that three related breeds from Scandinavia carry the same mutation. The affected dogs are homozygous for the GAA c.2237G>A mutation leading to a premature stop codon at amino acid position 746. The corresponding mutation has previously been reported in humans and causes infantile Pompe disease in combination with a second fully deleterious mutation. The affected dogs from both the Finnish as well as the Swedish breed mimic infantile-onset Pompe disease genetically, but also clinico-pathologically. Therefore this canine model provides a valuable tool for preclinical studies aimed at the development of gene therapy in Pompe disease.

Recent reports indicate that hepatitis C virus (HCV) may play a role in the pathogenesis of hepatocellular carcinoma in cirrhotics. Using an ELISA test, we evaluated the prevalence of anti-HCV antibodies in 97 patients with hepatocellular carcinoma (HCC) in cirrhosis and in a group of 223 patients, including: 49 patients with HBsAg-positive chronic liver disease (CLD), 42 with alcoholic CLD, 110 with cryptogenic CLD and 22 with post-transfusional HBsAg-negative CLD. All diagnoses were histologically confirmed. Overall, anti-HCV-positive HCC were 64% of the total, with no statistically significant difference with respect to CLD (60.9%). The prevalence of anti-HCV was higher in cryptogenic HCC (80%) than in HBsAg-positive (60%) or alcoholic HCC (42.8%) (p less than 0.005). When HCC and cirrhosis of similar putative etiology were considered, anti-HCV prevalence was significantly higher in HCC than in cirrhosis only in the groups of patients with alcoholic liver damage (60% in HCC vs. 38% in cirrhosis, p less than 0.005). In HBsAg-positive patients, anti-HCV prevalence was twice as high in HCC than in CLD, but the difference was not statistically significant. Overall, anti-HCV prevalence in HCC was significantly higher than in alcoholic or HBsAg-positive CLD (p less than 0.001 and p less than 0.01, respectively) but lower than in cryptogenic CLD (p less than 0.001). Association between anti-HCV and anti-HBc was significantly more prevalent in patients with CLD than in those with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by dermal-epidermal separation that is caused by mutations in the genes encoding hemidesmosomal components and laminin-5, the major epithelial adhesion ligand. Here, we report on the mutational analysis of LAMA3, LAMB3, and LAMC2 genes encoding laminin-5 chains in 19 Italian patients, 11 affected with the severe Herlitz (H JEB) and eight with the mild non-Herlitz variant of JEB (non-H JEB). Eighteen mutations, seven of which were novel, were identified and their consequences analyzed at the mRNA and protein level. Premature termination codon mutations in both alleles of LAMB3 or LAMC2 genes were found in nine of the 11 H JEB patients, with a prevalence of mutations in LAMC2. In one case, a homozygous frameshift mutation in LAMB3 was associated to illegitimate splicing leading to non-H JEB. One H JEB patient showed a large intragenic duplication within LAMC2, a genetic defect so far uncovered in laminin-5 genes. Splicing or missense mutations, were prevalent in non-H JEB patients. Collectively, five mutations appeared to be frequent in laminin-5 JEB patients: R635X, 29insC, E210K, W143X in LAMB3 and R95X in LAMC2. These recurrent mutations account for approximately 44% of laminin-5 JEB alleles in Italian patients.

Purpose : The aim of this investigation was to assess bone healing of sinus lift procedure in which the augmentation has been performed by using calcium sulphate like bone substitutes. The methods of this investigation how the use of Cone Beam Computed Tomography (CBCT) may be a valid instrument to support reconstructive surgery of the jaws. Patients and Methodology: 25 Patients presented large bone defects after tooth extractions located in the upper jaw posterior area. Vertical bone volume was assessed by CBCT examinations before and about six months after sinus lift surgery. Results: Examined defects treated with sinus lift surgery and evaluated by CBCT showed a strong increasing on the bone volume at 6 months follow up control. Conclusion: Calcium sulphate application in sinus lift surgery represent a safe and predictable option in the place of autologous bone. Therefore the application of CBCT investigation may give the clinicians the opportunity of evaluating with high precision value, the consistence of the bone defects before the surgery.