Cardiac arrest and left ventricular fibrosis in a Finnish family with the lamin A/C mutation

Introduction: We screened the candidate genes from a Finnish family in which the mother was resuscitated from ventricular fibrillation and the daughter died suddenly without any prior cardiac symptoms.
Methods and Results: In addition to screening of potential structural gene mutations, phenotyping of the proband and medico-legal autopsy of the victim of the sudden death, including histopathological examinations, were performed. Genetic screening revealed an R541C mutation in the lamin A/C gene both in the proband and her daughter. None of the 16 first- or second-degree relatives, or 96 unrelated healthy subjects, carried the same mutation. In the proband, the size and the global function of the left ventricle (LV) were normal, but a local hypokinesia and thinning of inferoposterior area of the LV were seen in 2D echocardiography and magnetic resonance imaging. Coronary angiogram and the results of the electrophysiological study were normal. Autopsy of the victim of sudden death showed localized thinning and fibrosis in the inferoposterior area of the LV, with only minimal fibrosis in the right ventricle and no abnormalities in the interventricular septum.
Conclusion: These observations indicate that a fatal or near-fatal cardiac arrhythmia can be the first clinical manifestation of a "de novo" mutation R541C of the lamin A/C gene. Replacement of cardiac myocytes by fibrosis seems to be the predominant pathologic-anatomic finding.     

Molecular characterization of HetRV8-ir1, a partitivirus of the invasive conifer pathogenic fungus Heterobasidion irregulare

The Heterobasidion annosum (Fr.) Bref. complex includes some of the most destructive conifer pathogenic fungi in the Boreal forest region. H. irregulare, formerly known as the North American pine type of H. annosum, was introduced from North America into Italy during the Second World War and occurs as an invasive pathogen in Pinus pinea stands together with the native European species H. annosum sensu stricto. We describe the complete nucleotide sequence of a new putative partitivirus from an Italian strain of H. irregulare. The bisegmented genome of HetRV8-ir1 encodes an RNA-dependent RNA polymerase of 704 aa and a capsid protein of 638 aa. The polymerase and capsid aa sequences are relatively similar (59-78 %) to those of Fusarium poae virus 1, Pleurotus ostreatus virus 1, and grapevine-associated partitivirus 1. HetRV8-ir1 is the first virus described from H. irregulare, and it is distantly related to previously known partitiviruses of Heterobasidion species.     

BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: Treatment response and evidence for nosocomial transmission

BackgroundBK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads.ObjectivesCharacterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment.Study designBy prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments).ResultsDecreasing BKV viremia of > 2 log₁₀ copies/mL and clinical resolution was seen in 4 patients over 5–12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patientsConclusionsThe data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir.     

Copy number alterations and neoplasia‐specific mutations in MELK,PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias

Genetic alterations affecting 9p are commonly present in many cancer types and many cancer‐related genes are located in this chromosomal region. We sequenced all of the genes located in a 32Mb region of 9p by targeted next generation sequencing (NGS) in 96 patients with different cancer types, including acute lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy number alterations (CNA), and mutations were studied from the NGS data. We detected a deletion at the CDKN2A locus as being the most frequent genetic alteration in all cancer types. In addition to this locus, NGS also identified other small regions of copy number loss and gain. However, different cancer types did not reveal any statistically significant differences with regard to CNA frequency or type. Of the 191 genes within the target region, two novel recurrent mutations were found in the MELK and PDCD1LG2 genes. The most commonly mutated gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1, and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted CDKN2A locus, we were able to identify a number of small deletions and gains, as well as novel recurrent mutations in different cancer types. © 2014 Wiley Periodicals, Inc.     

Effects of dental attendance frequency in heavy and low private care-using young adults

In Finland, adults born in 1961 or later were progressively entitled to subsidies for dental care from private practitioners during 1986-90, while at the same time having access to care in the Public Dental Service. The aim of this study was to compare the effects of attendance frequency of private dental care on treatment costs and treatment spectrum for the heaviest and lowest users over a period. Three separate cohorts of recipients of reimbursements were formed, using the Social Insurance Register. The highest and lowest cost groups in 1986, 1990, and 1994 were followed up to 1997. Initially, the mean numbers of visits were 1.2-1.3 and 5.2-5.6 and cost Euro 48-53 and Euro 358-379 among low users and heavy users, respectively, in all cohorts. Among the heavy users (the high-cost category) infrequent attendance was related to higher and frequent attendance to lower mean annual costs of care. Among the low users (the low-cost category) the opposite was true. Those who initially belonged to the high-cost category received in 1997 significantly more (P < 0.01) restorative treatment and, to a lesser extent, more (P < 0.01) preventive and periodontal treatment than those belonging to the low-cost category. Frequent dental care seemed to benefit those who received a lot of care. Frequency of attendance was not associated with being a low or a heavy user, indicating rigid check-up routines. The inclusion of simple oral health data would greatly improve the usefulness of the register as an evaluation tool for health-political decisions.