A Cautionary Tale of Hypertrophic Cardiomyopathy-From "Benign" Left Ventricular Hypertrophy to Stroke, Atrial Fibrillation, and Molecular Genetic Diagnostics: A Case Report and Review of Literature.

This case report concerns a 48-year-old man with a history of ischemic stroke at the age of 41 who reported cardiac hypertrophy, registered in his twenties when explained by increased physical activity. Family history was positive for a mother with permanent atrial fibrillation from her mid-thirties. At the age of 44, he had a first episode of persistent atrial fibrillation, accompanied by left atrial thrombosis while on a direct oral anticoagulant.

Successful Treatment With High-Dose Colchicine of a 101-Year-Old Patient Diagnosed With COVID-19 After an Emergency Cholecystectomy.

There are multiple factors associated with increased morbidity and mortality in COVID-19 patients, and advanced age is one such independent prognostic factor. It is well established that the multiorgan failure and death in COVID-19 patients are due to the hyperactivation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and the ensuing cytokine storm. Colchicine, a well-known anti-inflammatory drug, has been shown to inhibit the NLRP3 inflammasome in micromolar concentrations potently.

Colchicine-The Divine Medicine against COVID-19.

Colchicine has a number of effects that suggest it may be useful in the treatment of COVID-19. Myeloid cells are a major source of dysregulated inflammation in COVID-19. The hyperactivation of the NLRP3 inflammasome and the subsequent cytokine storm take place precisely inside them and can lead to multiorgan damage and death.

Effect of increasing doses of colchicine on the treatment of 333 COVID-19 inpatients.

Background: Previous research done in Bulgaria demonstrated a fivefold reduction in mortality from COVID-19 with increased doses of colchicine from two hospitals in the country. We report here a further 333 cases of COVID-19 inpatients, treated with different doses of colchicine and its effect on mortality.

Materials And Methods: A case-control comparison from two additional hospitals was conducted between increased doses of colchicine and added bromhexine to standard of care (SOC) versus current SOC.

High-Dose Colchicine: Key Factor in the Treatment of Morbidly Obese COVID-19 Patients.

Colchicine has long been known to possess anti-inflammatory effects by inhibiting microtubules, activation and migration of neutrophils, and most importantly, the inflammasome complex found in neutrophils and monocytes. Due to these properties, a number of clinical trials have tested the therapeutic effect of colchicine in COVID-19 patients. One common feature of these studies, however, is the low therapeutic dose used, which may explain the conflicting and disappointing results.

A Review of Stem Cell Attributes Derived from the Oral Cavity.

Oral cavity stem cells (OCSCs) have been the focus of intense scientific efforts due to their accessibility and stem cell properties. The present work aims to compare the different characteristics of 6 types of dental stem cells derived from the oral cavity: dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), stem cells from the apical papilla (SCAP), bone marrow mesenchymal stem cells (BMSC), and gingival mesenchymal stem cells (GMSC). Using immunofluorescence and real-time polymerase chain reaction techniques, we analysed the cells for stem cell, differentiation, adhesion, and extracellular matrix markers; the ability to proliferate in vitro; and multilineage differentiation potential.

High Doses of Colchicine Act As "Silver Bullets" Against Severe COVID-19.

A 48-year-old patient with a weight of 120 kg with type 2 diabetes mellitus, hypertension, and gout was hospitalized on the third day of the COVID-19 diagnosis. His general condition is relatively good, oxygen saturation is 89%. Despite starting standard treatment, on the seventh day from the onset of symptoms, the patient deteriorated sharply (oxygen saturation dropped to 74%).

MiRNA Signatures Related to Invasiveness and Recurrence in Patients With Non-Functioning Pituitary Neuroendocrine Tumors.

Purpose: This preliminary study aimed to analyze and identify differentially expressed miRNAs in Bulgarian patients with non-functioning pituitary neuroendocrine tumors (NFPitNET). The relationship between deregulated miRNAs and tumor invasiveness, recurrence, and size was determined.

Methods: Twenty patients with NFPitNET were selected and fresh pituitary tumor tissues were collected.

miRNAs and related genetic biomarkers according to the WHO glioma classification: From diagnosis to future therapeutic targets.

In the 2021 WHO classification of Tumors of the Central Nervous System, additional molecular characteristics have been included, defining the following adult-type diffuse glioma entities: Astrocytoma IDH-mutant, Oligodendroglioma IDH-mutant and 1p/19q-codeleted, and Glioblastoma IDH-wildtype. Despite advances in genetic analysis, precision oncology, and targeted therapy, malignant adult-type diffuse gliomas remain "hard-to-treat tumors", indicating an urgent need for better diagnostic and therapeutic strategies. In the last decades, miRNA analysis has been a hotspot for researching and developing diagnostic, prognostic, and predictive biomarkers for various disorders, including brain cancer.

Navigating the ALS Genetic Labyrinth: The Role of MAPT Haplotypes.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by wide clinical and biological heterogeneity, with a large proportion of ALS patients also exhibiting frontotemporal dementia (FTD) spectrum symptoms. This project aimed to characterize risk subtypes of the H1 haplotype within the (microtubule-associated protein tau) gene, according to their possible effect as a risk factor and as a modifying factor in relation to the age of disease onset. One hundred patients from Bulgaria with sporadic ALS were genotyped for the variants rs1467967, rs242557, rs1800547, rs3785883, rs2471738, and rs7521.

Effect of an Accidental Colchicine Overdose in a COVID-19 Inpatient With Bilateral Pneumonia and Pericardial Effusion.

A 32-year-old patient with COVID-19 pneumonia and pericardial effusion mistakenly took 15 mg of colchicine over 10 hours. He developed diarrhea that resolved two days after colchicine was stopped. Remarkably, this single overdose of colchicine, without any additional therapy, resulted in the complete recovery of bilateral pneumonia and pericardial effusion, and the patient was discharged on the hospital day 9th.

Novel insights on GTPBP3-associated hypertrophic cardiomyopathy.

About 100 genes have been associated with cardiomyopathies with genotype-phenotype correlations often hard to establish. Genetic testing may help to confirm the genetic diagnosis and assess the risk of inheritance in the family. A 25-year old male with hypertrophic cardiomyopathy and fasciculoventricular accessory pathway was referred for genetic testing by his cardiologist.

Arginase deficiency in Bulgaria: first cases and potential endemic region for the disorder.

Arginase deficiency is an autosomal recessive urea cycle disorder caused by pathogenic variants in the gene. The clinical features of the disease include spasticity, tremour, ataxia, hypotonia, microcephaly and seizures. Growth delay can also be observed in the affected individuals.

Complete, Rapid Resolution of Severe Bilateral Pneumonia and Acute Respiratory Distress Syndrome in a COVID-19 Patient: Role for a Unique Therapeutic Combination of Inhalations With Bromhexine, Higher Doses of Colchicine, and Hymecromone.

An otherwise healthy, 35-year-old man was hospitalized for the management of acute respiratory failure due to coronavirus disease 2019 (COVID-19)-related severe bilateral pneumonia and acute respiratory distress syndrome (ARDS). The patient therapeutic regimen included the widely accepted standard combination of oxygen, anticoagulation therapy; corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), and antibiotics. A novel combination of colchicine, hymecromone, and bromhexine inhalations was added to the therapeutic regimen as part of our unique COVID-19 management institutional protocol.

Role of endothelial dysfunction in the severity of COVID‑19 infection (Review).

COVID‑19 patients with severe infection have been observed to have elevated auto‑antibodies (AAs) against angiotensin II receptor type 1 (AT1R) and endothelin (ET) 1 receptor type A (ETAR), compared with healthy controls and patients with favorable (mild) infection. AT1R and ETAR are G protein‑coupled receptors, located on vascular smooth muscle cells, fibroblasts, immune and endothelial cells, and are activated by angiotensin II (Ang II) and ET1 respectively. AAs that are specific for these receptors have a functional role similar to the natural ligands, but with a more prolonged vasoconstrictive effect.

MiRNA expression profiling in adenocarcinoma and squamous cell lung carcinoma reveals both common and specific deregulated microRNAs.

The current study investigated the expression signatures of miRNAs in lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC). miRNA profiling was performed using microarray in 12 LUAD and 12 LUSC samples and adjacent normal tissues. In LUAD, 107 miRNAs were significantly deregulated, whereas 235 miRNAs were deregulated in LUSC.

Diagnostic, grading and prognostic role of a restricted miRNAs signature in primary and metastatic brain tumours. Discussion on their therapeutic perspectives.

At present, brain tumours remain one of the "hard-to-treat" malignancies with minimal improvement in patients' survival. Recently, miRNAs have been shown to correlate with oncogenesis and metastasis and have been investigated as potential biomarkers for diagnosis, prognosis and therapy prediction in different brain malignancies. The aim of the current study was to select an accurate and affordable brain tumour detection and grading approach.

A pilot study reveals the potential of miR-31-3p and miR-196a-5p as non-invasive biomarkers in advanced laryngeal cancer.

Introduction: Recently, miRNAs have become popular molecules used as non-invasive biomarkers in cancer diseases.

Aim: The aim of the study was to explore the expression of four miRNAs isoforms: miR-31-3p, miR-196a-5p, miR-210-3p and miR-424-5p in plasma and tissue samples from patients with advanced laryngeal squamous cell carcinoma (LSCC) and healthy controls.

Materials And Methods: Fresh-frozen tumour and normal laryngeal tissue as well as plasma samples were obtained from 22 patients diagnosed with advanced LSCC.

Characterization of population genetic structure of hereditary transthyretin amyloidosis in Bulgaria.

The hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an autosomal dominant genetic disease characterized by amyloid formation in different tissues due to pathogenic variants in the gene. Great heterogeneity in the penetrance and manifestation of ATTRv amyloidosis is observed. In Bulgaria, the most common pathogenic variant is .

MYH7-related disorders in two Bulgarian families: Novel variants in the same region associated with different clinical manifestation and disease penetrance.

Pathogenic variants in MYH7 cause a wide range of cardiac and skeletal muscle diseases with childhood or adult onset. These include dilated and/or hypertrophic cardiomyopathy, left ventricular non-compaction cardiomyopathy, congenital myopathies with multi-minicores and myofiber type disproportion, myosin storage myopathy, Laing distal myopathy and others (scapulo-peroneal or limb-girdle muscle forms). Here we report the results from molecular genetic analyses (NGS and Sanger sequencing) of 4 patients in two families with variable neuromuscular phenotypes with or without cardiac involvement.

SCN1A mutation spectrum in a cohort of Bulgarian patients with GEFS+ phenotype.

Background: Dravet syndrome (DS) is the most severe form of Generalized Epilepsy with Febrile Seizures plus (GEFS+) syndrome with a clear genetic component in 85% of the cases. It is characterized by fever-provoked seizure onset around six months of age and subsequent developmental deterioration later in life.

Methods: In the current study, 60 patients with fever-provoked seizures and suspicion either of GEFS+ (50 patients) or of DS (10 patients) were referred for SCN1A gene sequence analysis.

The Role of miRNAs and lncRNAs in Laryngeal Squamous Cell Carcinoma - a Mini-Review.

Laryngeal squamous cell carcinoma is a common malignancy in men. Bulgaria is one of the countries in Europe with the highest incidence and mortality rates of the aggressive, severe disease of laryngeal cancer. Proven etiological factors are the abuse of tobacco and alcohol beverages.

Peripheral myelin protein 2 - a novel cluster of mutations causing Charcot-Marie-Tooth neuropathy.

Background: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder characterized by wide clinical, genetic and pathomechanistic heterogeneity. Recently, the gene encoding peripheral myelin protein 2 (PMP2) was identified as a novel cause for CMT neuropathy with three mutations that structurally cluster together (p.Ile43Asn, p.

Founder effect of the Glu89Gln mutation in the Bulgarian population.

Hereditary transthyretin amyloidosis is an autosomal dominant genetic disorder caused by missense mutations in the gene resulting in amyloid formation of the transthyretin protein. Depending on the system affection, the manifestations may be different and high heterogeneity in the penetrance is observed. An endemic region in Bulgaria exists where the mutation Glu89Gln is found with high frequency.