The Prevalence and Genetic Characterization of Human Metapneumovirus in Bulgaria, 2016-2019.

INTRODUCTION: We investigated the prevalence of human metapneumovirus (hMPV) among patients with acute respiratory infections in Bulgaria, and performed genetic characterization of the F gene of these strains. METHODS: Nasopharyngeal swabs collected from patients of a range of ages were tested by using real-time PCR for 12 respiratory viruses. The F gene was sequenced, and phylogenetic and amino acid analyses of the F gene/protein were performed. RESULTS: A total of 1,842 patients were examined during a 3-year period; 1,229 patients (66.7%) were positive for at least one respiratory virus. hMPV was identified in 83 (4.5%) patient samples. Eleven (13%) of hMPV-positive patients were coinfected with another respiratory virus. The hMPV incidence rate in the 2016/2017, 2017/2018, and 2018/2019 winter seasons was 5.4, 5.4, and 3.1%, respectively. hMPV was mainly detected in specimens collected between January and May (89.2% of cases). The incidence of hMPV infection was highest (5.1%) among the youngest age-group (0-4 years), where hMPV was a causative agent in 8.1 and 4.8% of bronchiolitis and pneumonia cases, respectively. Among the patients aged ≥5 years, hMPV was detected in 2.2 and 3.2% of cases of pneumonia and central nervous system infections, respectively. Phylogenetic analysis of the F gene showed that the sequenced hMPV strains belonged to the A2b, B1, and B2 genotypes. Numerous amino acid substitutions were identified compared with the NL00/1 prototype strain. CONCLUSION: This study revealed the significant role of hMPV as a causative agent of serious respiratory illnesses in early childhood, and also demonstrated year-to-year changes in hMPV prevalence and genetic diversity in circulating strains.

Somatic clones heterozygous for recessive disease alleles of BMPR1A exhibit unexpected phenotypes in Drosophila.

The majority of mutations studied in animal models are designated as recessive based on the absence of visible phenotypes in germline heterozygotes. Accordingly, genetic studies primarily rely on homozygous loss-of-function to determine gene requirements, and a conceptually-related 'two-hit model' remains the central paradigm in cancer genetics. Here we investigate pathogenesis due to somatic mutation in epithelial tissues, a process that predominantly generates heterozygous cell clones. To study somatic mutation in Drosophila, we generated inducible alleles that mimic human Juvenile polyposis-associated BMPR1A mutations. Unexpectedly, four of these mutations had no phenotype in heterozygous carriers but exhibited clear tissue-level effects when present in somatic clones of heterozygous cells. We conclude that these alleles are indeed recessive when present in the germline, but nevertheless deleterious when present in heterozygous clones. This unforeseen effect, deleterious heteromosaicism, suggests a 'one-hit' mechanism for disease initiation that may explain some instances of pathogenesis associated with spontaneous mutation.

Delayed right atrial lateral electromechanical coupling relative to the septal one can be associated with paroxysmal atrial fibrillation.

BACKGROUND: Non-invasive prediction of paroxysmal atrial fibrillation (PAF) is one of the most recent interests of cardiology. AIM: The current study investigates the relationship between the atrial electromechanical coupling time (EMCT) and PAF. PATIENTS AND METHODS: A group of 35 patients with PAF was compared with a group of 37 subjects without PAF. Pulsed wave tissue Doppler evaluations of atrial walls were performed from apical four chambers view under ECG monitoring. The time intervals from the onset of P wave to the onset of late diastolic wave (A') at right atrial wall (P-RA), interatrial septum (P-IAS), and left atrial wall (P-LA, maximum EMCT) were measured. The right atrial EMCT (P-RA minus P-IAS), left atrial EMCT (P-LA minus P-IAS) and interatrial EMCT (P-LA minus P-RA) were computed. A' wave velocities were measured from each atrial wall. RESULTS: RA (16.0±13.1 vs. -8.7±18.6 ms, p < 0.001) and maximum (91.5±32.6 vs. 72.0±23.1 ms, p = 0.001) EMCT were longer, RA A' velocity was higher in the patient group. There were no differences between the groups in LA and interatrial EMCT, and septal and LA A' velocities. Regression analysis revealed that only RA [OR: 1.148 (1.041-1.267), p = 0.006] and maximum [OR: 1.099 (1.009-1.197), p = 0.031] EMCT were independent variables for PAF. In order to predict patients with PAF, we have chosen +7.5 msn for the RA EMCT which yielded 69% sensitivity and 71.4% specificity to predict patients. CONCLUSIONS: Delayed RA lateral EMCT relative to septal one and delayed maximum EMCT detected by tissue Doppler could be a valuable method for identifying patients with PAF.

Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer.

Cell death is a fundamental ingredient of life. Thus, not surprisingly more than one form of cell death exists. Several excellent reviews on various forms of cell death have already been published but manuscripts describing interconnection and interdependence between such processes are uncommon. Here, what follows is a brief introduction on all three classical forms of cell death, followed by a more detailed insight into the role of p53, the master regulator of apoptosis, and other forms of cell death. While discussing p53 and also the role of caspases in cell death forms, we offer insight into the interplay between autophagy and apoptosis, or necrosis, where autophagy may initially serve pro-survival functions. The review moves further to present some details about less researched forms of programmed cell death, namely necroptosis, necrosis and mitoptosis. These "mixed" forms of cell death allow us to highlight the interconnected nature of cell death forms, particularly apoptosis and necrosis. The interdependence between apoptosis, autophagy and necrosis, and their significance for cancer development and treatment are also analyzed in further parts of the review. In the concluding parts, the afore-mentioned issues will be put in perspective for the development of novel anti-cancer therapies.

Isolated tricuspid valve prolapsed: identification using two- and three-dimensional echocardiography and transoesophageal echocardiography.

We present a case of isolated prolapse of the tricuspid anterior leaflet in an asymptomatic 34-year-old man who was referred to our hospital for a routine check up. We performed two-and three-dimensional transoesophageal echocardiography (TEE). We found three-dimensional TEE a useful, non-invasive tool that can provide additional information to two-dimensional echocardiography in the assessment of tricuspid valve prolapse.