Cocirculation of Hajj and non-Hajj strains among serogroup W meningococci in Italy, 2000 to 2016

In Italy, B and C are the predominant serogroups among meningococci causing invasive diseases. Nevertheless, in the period from 2013 to 2016, an increase in serogroup W Neisseria meningitidis (MenW) was observed. This study intends to define the main characteristics of 63 MenW isolates responsible of invasive meningococcal disease (IMD) in Italy from 2000 to 2016. We performed whole genome sequencing on bacterial isolates or single gene sequencing on culturenegative samples to evaluate molecular heterogeneity. Our main finding was the cocirculation of the Hajj and the South American sublineages belonging to MenW/ clonal complex (cc)11, which gradually surpassed the MenW/cc22 in Italy. All MenW/cc11 isolates were fully susceptible to cefotaxime, ceftriaxone, ciprofloxacin, penicillin G and rifampicin. We identified the fulllength NadA protein variant 2/3, present in all the MenW/cc11. We also identified the fHbp variant 1, which we found exclusively in the MenW/cc11/Hajj sublineage. Concern about the epidemic potential of MenW/cc11 has increased worldwide since the year 2000. Continued surveillance, supported by genomic characterisation, allows high-resolution tracking of pathogen dissemination and the detection of epidemicassociated strains

Naming Genes for Dystonia: DYT-z or Ditzy?

Dystonias are a clinically and etiologically diverse group of disorders. Numerous genes have now been associated with different dystonia syndromes, and multiple strategies have been proposed for how these genes should be lumped and split into meaningful categories. The traditional approach has been based on the Human Genome Organization’s plan for naming genetic loci for all disorders. For dystonia this involves a DYT prefix followed by a number (e.g., DYT1, DYT2, DYT3, etc.). A more recently proposed approach involves assigning multiple prefixes according to the main elements of the phenotype (e.g., DYT, PARK, CHOR, TREM, etc.) followed by the name of the responsible gene. This article describes these nomenclature systems and summarizes some of their limitations. We focus on dystonia as an example, although the concepts may be applied to all movement disorders

Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study

BACKGROUND: Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice. METHODS: A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18–40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients. RESULTS: At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others. CONCLUSIONS: Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide information on the most relevant items to be considered when conducting cost-effectiveness studies comparing specific alternatives for the treatment of target patients

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia.

Dystonia type 4 (DYT4) was first described in a large family from Heacham in Norfolk with an autosomal dominantly inherited whispering dysphonia, generalized dystonia, and a characteristic hobby horse ataxic gait. We carried out a genetic linkage analysis in the extended DYT4 family that spanned 7 generations from England and Australia, revealing a single LOD score peak of 6.33 on chromosome 19p13.12-13. Exome sequencing in 2 cousins identified a single cosegregating mutation (p.R2G) in the β-tubulin 4a (TUBB4a) gene that was absent in a large number of controls. The mutation is highly conserved in the β-tubulin autoregulatory MREI (methionine-arginine-glutamic acid-isoleucine) domain, highly expressed in the central nervous system, and extensive in vitro work has previously demonstrated that substitutions at residue 2, specifically R2G, disrupt the autoregulatory capability of the wild-type β-tubulin peptide, affirming the role of the cytoskeleton in dystonia pathogenesis

Fatal Clostridium perfringens Septicemia After Colonoscopic Polypectomy, Without Bowel Perforation

Since its introduction, colonoscopy has played an important role as a diagnostic, therapeutic, and screening tool. In general, colonoscopy is regarded as a safe procedure, but complications may occur. The most dreaded of these complications is colonic perforation. Bacteremia postprocedure may occur, and although it is not uncommon, it rarely results in clinically significant complications. Patients with IBD (inflammatory bowel disease) are a high-risk population for bacteremia, which may leads to bowel wall overstepping by the bacteria. With regard to that, we report a fatal case of gas gangrene complicating colonoscopy polypectomy without bowel perforation in a healthy adult. To the best of our knowledge, only two other cases of retroperitoneal gas gangrene associated with colonoscopy polypectomy without bowel perforation have been described in international literature, but none of which was completed by a molecular biology analysis

Genetic susceptibility to aspergillosis in allogeneic stem-cell transplantation

Invasive aspergillosis (IA) is a major threat to positive outcomes for allogeneic stem-cell transplantation (allo-SCT) patients. Despite presenting similar degrees of immunosuppression, not all individuals at-risk ultimately develop infection. Therefore, the traditional view of neutropenia as a key risk factor for aspergillosis needs to be accommodated within new conceptual advances on host immunity and its relationship to infection. Polymorphisms in innate immune genes, such as those encoding TLRs, cytokines and cytokine receptors, have recently been associated with susceptibility to IA in allo-SCT recipients. This suggests that understanding host-pathogen interactions at the level of host genetic susceptibility will allow the formulation of new targeted and patient-tailored antifungal therapeutics, including improved donor screening.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/65962/2009, SFRH/BPD/46292/2008Specific Targeted Research Projects MANASP (LSHE-CT-2006), contract number 037899 (FP6), Italian Project PRIN2007KLCKP8_004

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results:Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions:The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss