Impact of Demographic Features, Lifestyle, and Comorbidities on the Clinical Expression of Hypertrophic Cardiomyopathy.

No abstract

Chromosomal assignment of the ovine hairless (hr) gene by fluorescence in situ hybridization.

Congenital hypotrichosis in mammalian species consists of partial or complete absence of a hair coat at birth. Affected individuals having a partial hair coat at birth may loose it subsequently.The aim of this paper was to physically map the ovine hr gene using fluorescence in situ hybridization (FISH).A preliminary study on an internet data bank (http://www.informatics.jax.org) showed that the regions of the hr gene on murine chromosome 14 and human chromosome 8 present homology with ovine chromosome 2

Survey of milk protein polymorphism in the "Bovina Rossa Siciliana"

The “Rossa Siciliana” is an autochthonous small Sicilian dairy cattle population, accounting for 5-7,000 individuals.This breed is characterized by high ability to live on poor pasture lands, moderate milk production, and traditionally linked to cheese production. Aim of this work was to investigate milk protein polymorphisms in this population. A total of 62 individual milk samples were collected from 19 extensive farms spread in the “Parco dei Nebrodi” area (Messina). All samples were analyzed by isoelectrofocusing (IEF) with pH range 2.5-6. High variability was found at the CSN1S1, CSN2, CSN3, LGB and LALBA loci, while the CSN1S2 locus was monomorphic for the A allele. The allele frequencies and the Hardy-Weinberg equilibrium were estimated using the GENEPOP software, further the casein haplotype frequencies and the occurrence of the linkage disequilibrium were computed with the EH software, taking into account the association among loci. Joint analysis at all loci showed that the population is not in Hardy-Weinberg equilibrium (Chi-square=19.0, pvalue=0.0407), probably due to genetic drift. Of the three alleles detected at CSN1S1 locus, CSN1S1*B and CSN1S1*C had high frequencies (0.734 and 0.258 respectively), as reported for most breeds. The CSN1S1*D allele was detected with a low frequency (0.008). High frequencies were found for CSN2*A2 (0.573) and CSN3*B (0.637). High frequencies were observed for LALBA*B (0.903) and LGB*B (0.815). Strong linkage disequilibrium was detected for the polymorphic casein loci CSN1S1-CSN2-CSN3. For the casein haplotype only the hypothesis of association among loci was considered. Out of the 27 expected, only four haplotypes had a frequency higher than 0.10. The most frequent haplotype was BA2B (0.236), followed by CA2B (0.214), BA1A (0.168), BA1B (0.131), and BA2A (0.094). The high frequency of BA2B haplotype and the possible relation with production traits are under investigation

Comparison of different calculation techniques for absorbed dose assessment in patient specific peptide receptor radionuclide therapy

Aim: The present work concerns the comparison of the performances of three systems for dosimetry in RPT that use different techniques for absorbed dose calculation (organ-level dosimetry, voxel-level dose kernel convolution and Monte Carlo simulations). The aim was to assess the importance of the choice of the most adequate calculation modality, providing recommendations about the choice of the computation tool. Methods: The performances were evaluated both on phantoms and patients in a multi-level approach. Different phantoms filled with a 177Lu-radioactive solution were used: a homogeneous cylindrical phantom, a phantom with organ-shaped inserts and two cylindrical phantoms with inserts different for shape and volume. A total of 70 patients with NETs treated by PRRT with 177Lu-DOTATOC were retrospectively analysed. Results: The comparisons were performed mainly between the mean values of the absorbed dose in the regions of interest. A general better agreement was obtained between Dose kernel convolution and Monte Carlo simulations results rather than between either of these two and organ-level dosimetry, both for phantoms and patients. Phantoms measurements also showed the discrepancies mainly depend on the geometry of the inserts (e.g. shape and volume). For patients, differences were more pronounced than phantoms and higher inter/intra patient variability was observed. Conclusion: This study suggests that voxel-level techniques for dosimetry calculation are potentially more accurate and personalized than organ-level methods. In particular, a voxel-convolution method provides good results in a short time of calculation, while Monte Carlo based computation should be conducted with very fast calculation systems for a possible use in clinics, despite its intrinsic higher accuracy. Attention to the calculation modality is recommended in case of clinical regions of interest with irregular shape and far from spherical geometry, in which Monte Carlo seems to be more accurate than voxel-convolution methods

Molecular cloning and nucleotide sequence of cDNA encoding the entire precursor of rat liver medium chain acyl coenzyme A dehydrogenase.

cDNA encoding the precursor of rat liver medium chain acyl-CoA dehydrogenase (EC 1.3.99.3) was cloned and sequenced. The longest cDNA insert isolated was 1866 bases in length. This cDNA encodes the entire protein of 421-amino acids including a 25-amino acid leader peptide and a 396-amino acid mature polypeptide. The identity of the medium chain acyl-CoA dehydrogenase clone was confirmed by matching the amino acid sequence predicted from the cDNA to the NH2-terminal and nine internal tryptic peptide sequences derived from pure rat liver medium chain acyl-CoA dehydrogenase. The calculated molecular masses of the precursor medium chain acyl-CoA dehydrogenase, the mature medium chain acyl-CoA dehydrogenase, and the leader peptide are 46,600, 43,700, and 2,900 daltons, respectively. The leader peptide contains five basic amino acids and only one acidic amino acid; thus, it is positively charged, overall. Cysteine residues are unevenly distributed in the mature portion of the protein; five of six are found within the NH2-terminal half of the polypeptide. Comparison of medium chain acyl-CoA dehydrogenase sequence to other flavoproteins and enzymes which act on coenzyme A ester substrates did not lead to unambiguous identification of a possible FAD-binding site nor a coenzyme A-binding domain. The sequencing of other homologous acyl-CoA dehydrogenases will be informative in this regard

Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death

All talk and no action: a transcranial magnetic stimulation study of motor cortex activation during action word production

A number of researchers have proposed that the premotor and motor areas are critical for the representation of words that refer to actions, but not objects. Recent evidence against this hypothesis indicates that the left premotor cortex is more sensitive to grammatical differences than to conceptual differences between words. However, it may still be the case that other anterior motor regions are engaged in processing a word's sensorimotor features. In the present study, we used single- and paired-pulse transcranial magnetic stimulation to test the hypothesis that left primary motor cortex is activated during the retrieval of words (nouns and verbs) associated with specific actions. We found that activation in the motor cortex increased for action words compared with non-action words, but was not sensitive to the grammatical category of the word being produced. These results complement previous findings and support the notion that producing a word activates some brain regions relevant to the sensorimotor properties associated with that word regardless of its grammatical category