The smoker's paradox during the COVID-19 pandemic? The influence of smoking and vaping on the incidence and course of SARS-CoV-2 virus infection as well as possibility of using nicotine in the treatment of COVID-19 - Review of the literature.

AIM OF THE STUDY: The study aims to present the current state of knowledge on the impact of traditional cigarettes and the nicotine contained in them on the incidence and course of SARS-CoV-2 infection. Moreover, we decided to exhibit the possibility of using this substance to treat COVID-19 infections. MATERIAL AND METHODS: The latest available scientific publications were reviewed until November 14, 2020, from the PubMed platform. RESULTS: Nicotine is a cholinergic agonist and pro-inflammatory cytokines inhibitor. Some authors present that smoking and nicotine reduce the amount of the ACE2 receptors which are used by the novel coronavirus to enter cells, while others claim that ACE2 receptors are upregulated in smokers. Moreover, the interaction of SARS-CoV-2 with nAChR is suspected of dysregulation of the nicotinic cholinergic system, which is associated with the pathophysiology of COVID-19. Due to the harmfulness of cigarettes, a high frequency of smokers is suspected among people suffering from COVID-19. However, some studies report that the number of current smokers hospitalized for SARS-CoV-2 infection is lower than expected, considering the prevalence of smoking in individual countries. Nicotine could restore the impaired function of the nicotine cholinergic system and possibly mitigate the cytokine storm. CONCLUSIONS: There is no clear attitude regarding the impact of smoking on the new coronavirus infection now. Researchers do not recommend smoking as a tool to combat the pandemic and show the importance of fighting addiction to reduce the adverse health effects of smoking. Both the relationship between cigarettes and the morbidity and severity of COVID-19, as well as the possibility of using nicotine in the treatment of the disease, require further analysis.

The influence of vaccination against tuberculosis with the Bacillus-Calmette-Guérin(BCG) vaccine on COVID-19 incidence and mortality - review of the literature.

THE AIM OF THE STUDY: Is to present the state of knowledge from April and May 2020 about the influence of Bacillus-Calmette-Guérin vaccination against tuberculosis on incidence and mortality due to COVID-19. MATERIAL AND METHODS: A review of the latest literature till 9 May 2020 has been made. PubMed and ResearchGate databases and WHO reports were used. RESULTS: Immunomodulatory properties of the tuberculosis vaccine which protects against severe cases of tuberculosis and partly against other infections are indicated, including viral and respiratory infections. The BCG vaccine induces heterologous immunity and trained innate immunity. It was noted that in countries which maintain obligatory BCG vaccination COVID-19 incidence and mortality are lower than in countries that have stopped or never introduced BCG as mandatory vaccination. Most analysis confirmed this relationship, but they indicated the possible impact of other factors, such as genetics in the population, the type of strain from BCG vaccine, the level of health care and the wealth of a nation, the structure of migration, co-morbidities and a policy of introducing social distance. CONCLUSIONS: At the moment, we do not have enough evidence to support or deny the hypothesis of COVID-19 reduction in incidence and mortality in countries maintaining obligatory BCG vaccination. Other factors that might affect the results should be considered in further analysis. The results of clinical trials will provide more reliable proofs than analysis of epidemiological data. WHO does not recommend BCG vaccination to prevent COVID-19 and recommends it to newborns from areas with a higher incidence of tuberculosis.

Impact of level of vitamin D in the body on the severity of COVID-19 - review of the literature.

INTRODUCTION: The aim of the study is to present the current state of knowledge on the influence of vitamin D levels on the severity of the course of COVID-19. MATERIAL AND METHODS: The latest available literature was reviewed until October 30, 2020 from the PubMed database. RESULTS: The literature reports that vitamin D has immunomodulatory and anti-inflammatory effects. It reduces the expression of cytokines such as IL-6, TNF-α and INF-γ, regulates the activity of T helper lymphocytes, and other elements of the immune system at the molecular level. The deficiency of this vitamin promotes the activation of the renin-angiotensin-aldosterone system, contributing to the development of acute respiratory distress syndrome. The severity of the course of SARS-CoV-2 infection depends on comorbidities, the development and course of which may also be affected by vitamin D levels (coagulopathies, pulmonary, cardiological, metabolic diseases). Most of the analyzed research studies from different countries indicated a relationship between insufficient vitamin D levels and a more severe course of COVID-19 and an increase in mortality due to it, especially among the elderly. Researchers agree that further analyzes are necessary concerning both the influence of the vitamin D blood serum levels on the morbidity and mortality due to COVID-19 as well as the use of its supplementation in the struggle against SARS-CoV-2 virus. There are reports of possible beneficial interactions of vitamin D with other substances, such as quercetin, estradiol, some microelements, and other vitamins. CONCLUSIONS: Maintaining an adequate level of vitamin D has a positive effect on the functioning of the immune system. At the moment, there is insufficient evidence to establish a clear relationship between vitamin D levels and the severity of COVID-19. It is necessary to conduct further research on a larger study group. The literature does not mention the use of vitamin D as a medication for COVID-19. People at risk of vitamin D deficiency should consider vitamin D supplementation at the current time of the pandemic.

Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria (KIT, ADAMTS13, GBA1, and PIG-A genes, respectively). In Castleman disease, improper ETS1, PTPN6, TGFBR2, DNMT3A, and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF, MAP2K1, MAP3K1, ARAF, ERBB3, NRAS, KRAS, PICK1, PIK3R2, and PIK3CA. Genes like HPLH1, PRF1, UNC13D, STX11, STXBP2, SH2D1A, BIRC4, ITK, CD27, MAGT1, LYST, AP3B1, and RAB27A are possible reasons for hemophagocytic lymphohistiocytosis. Among novel molecular medicines, tyrosine kinase inhibitors, mTOR inhibitors, BRAF inhibitors, interleukin 1 or 6 receptor antagonists, monoclonal antibodies, and JAK inhibitors are examples of drugs expanding therapeutic possibilities. An explanation of the molecular basis of rare diseases might lead to a better understanding of the pathogenesis and prognosis of the disease and may allow for the development of new molecularly targeted therapies.

Diagnostic approach to a paediatric patient with Wiedemann-Steiner syndrome with de novo missense variant in the KMT2A gene - a case report.

INTRODUCTION: Wiedemann-Steiner syndrome is caused by mutations in the KMT2A gene (11q23.3). It might be inherited autosomal dominant or appear de novo. Features described in the syndrome include developmental delay, short stature, hypotonia, hypertrichosis, facial dysmorphic features, and intellectual disability. CASE REPORT: A boy aged 5.5 months was admitted to the Genetics Outpatient Clinic due to delayed psychomotor development. Microsomia, hypotonia, joint laxity, and facial dysmorphic features were noticed. No genomic imbalance was found in microarray, based on comparative genomic hybridization. The c.3528G>T variant of the KMT2A gene was identified on chromosome 11 of the missense type in next-generation sequencing. The reasons for phenotypic features were confirmed in genetic research. CONCLUSIONS: Wiedemann-Steiner syndrome has a variable clinical phenotype. There is a strong need to pay attention to phenotypic features that may suggest the syndrome and refer patients for appropriate genetic diagnostics.

Impact of Triclosan on Female and Male Reproductive System and Its Consequences on Fertility: A Literature Review.

Objective: Triclosan is an aromatic organic compound with antibacterial and fungicidal properties, most often used in soaps, toothpaste and other cosmetics. The study aimed to analyze the influence of triclosan on the female and male reproductive systems and the consequences on fertility. Materials and methods: A review of the latest literature derived from PubMed and Google Scholar platforms has been made. After following the search strategy, applying inclusion criteria and analysis of the obtained results assessed by two independent analysts, 45 studies were included in the review. Results: Due to the similar structure of triclosan (TCS) to anthropogenic estrogens, TCS can interact with hormone receptors, affect hormone balance, and influence reproductive health and carcinogenesis. It has been noted that TCS might affect luteal cell progesterone production and disrupt ovarian function. Prenatal exposure to the chemical can have an impact on the reproductive system of newborns. TCS might be a risk factor for endometrial physiology and impair reproduction. TCS negatively affects the male reproductive system via interrupting steroidogenesis mediated miRNA (micro-ribonucleic acid) pathways. Negative effects of TCS on early development and embryogenesis in animals were evidenced. Moreover, TCS has the potential to promote carcinogenesis in human breast, ovarian, and prostate cells. Conclusion: Potential impact of TCS on the reproductive system raises concern about its safety, due to its similar structure to anthropogenic estrogens and detection in the environment. TCS-induced disruption of hormone levels in the female and male reproductive systems may be the cause of impaired reproductive health, resulting in subfertility. Further investigations are required to evaluate the mechanisms and effect of TCS on human reproductive health.

Hypodiploidy in a pediatric patient of T-cell acute lymphoblastic leukemia: a case report.

BACKGROUND: T-cell acute lymphoblastic leukemia is a subtype of acute lymphoblastic leukemia, one of the most common childhood neoplasms. Hypodiploidy is a chromosome abnormality with fewer than 45 chromosomes and is associated with unsatisfactory clinical outcomes in acute lymphoblastic leukemia. CASE PRESENTATION: We report clinical and genetic findings of a 14-year-old male with T-cell acute lymphoblastic leukemia with low-hypodiploidy. The medical history included neck pain for a month, facial nerve palsy on the right side for 6 days, fever, drowsiness, and weakness for 3 days, vomiting, diarrhea for 1 day. The physical examination presented features of hypovolemia, palsy of the facial nerve on the right side, enlarged lymph nodes, hepatosplenomegaly, sore throat, and petechiae of the skin. Radiological images indicated lesions of different organs. Bone marrow biopsy confirmed precursor T-ALL. In the FISH tests, KMT2A and BCR/ABL1 rearrangements were not observed. GTG banding revealed 3 cell clones, which confirmed the hypodiploidy. Multiplex RT-qPCR was performed. STIL/TAL1 (del1p32) gene rearrangement was found in the blast cells. Additional tests were performed using the CytoScan HD microarray technique. Molecular karyotype did not reveal hypodiploidy, but identified other abnormalities such as duplication of chromosomal regions: 4q25q35.2, 6p23.3p11.1 and 8p23.3q24.21, and the loss of heterozygosity of short arm chromosome 9. In two regions of the chromosome biallelic deletions were found at 9p21.3, including the CDKN2A, CDKN2B, IFNA1, MTAP genes and at 10q23.31, containing PTEN. The child died 9 days after diagnosis. CONCLUSIONS: Bone marrow biopsy, GTG banding, FISH techniques, and molecular karyotyping were used to make an accurate diagnosis. This case documents a rapid progression of the disease and unfavorable results of T-cell acute lymphoblastic leukemia with hypodiploidy.

Effect of Spirulina Supplementation on Systolic and Diastolic Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Spirulina is a microalga that presents various important pro-health properties, for instance lowering blood pressure in the research. The study aims to appraise the efficacy of Spirulina administration on systolic (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved by a systematic search of PubMed, Web of Science, and the Cochrane Library databases from inception to June 2021 according to a standardized protocol. The effect size of each study was counted from mean and standard deviation before and after the intervention and shown as Un-standardized mean difference and 95% confidence interval. Sensitivity analyses were performed. Meta-analysis on 5 RCTs with 230 subjects was eligible. The amount of Spirulina ranged from 1 to 8 g per day, and intervention durations ranged from 2 to 12 weeks. Data analysis indicated that Spirulina supplementation led to a significant lowering of SBP (Mean Difference (MD): -4.59 mmHg, 95% Confidence Interval (CI): -8.20 to -0.99, I square statistic (I2) = 65%) and significant lowering of DBP (MD: -7.02 mmHg, CI: -8.86 to -5.18, I2 = 11%), particularly in a subgroup of hypertensive patients. Spirulina administration might have a supportive effect on the prevention and treatment of hypertension. More exact randomized controlled trials are needed to clarify the effect of Spirulina supplementation on blood pressure.

Three case reports of patients indicating the diversity of molecular and clinical features of 16p11.2 microdeletion anomaly.

BACKGROUND: 16p11.2 microdeletion is a known chromosomal anomaly associated mainly with neurocognitive developmental delay, predisposition to obesity, and variable dysmorphism. Although this deletion is relatively rare among the general population, it is one of the serious known genetic aetiologies of obesity and autism spectrum disorder. CASE PRESENTATION: This study presents three cases of deletions within the 16p11.2 region. Every child had mild variable craniofacial abnormalities, hand or foot anomalies and developmental and language delays. The first proband had obesity, epilepsy, moderate intellectual disability, aphasia, motor delay, hyperinsulinism, and café au lait spots. The second proband suffered from cardiac, pulmonary, and haematological problems. The third proband had motor and language delays, bronchial asthma, and umbilical hernia. Although each patient presented some features of the syndrome, the children differed in terms of their clinical pictures. Genetic diagnosis of 16p11.2 microdeletion syndrome was made in children at different ages based on multiplex ligation probe-dependent amplification analysis and/or microarray methods. CONCLUSIONS: Our reports allow us to analyse and better understand the biology of 16p11.2 microdeletion throughout development. However, the variability of presented cases supports the alternate conclusion to this presented in available literature regarding 16p11.2 deletion, as we observed no direct cause-and-effect genotype/phenotype relationships. The reported cases indicate the key role of the interdisciplinary approach in 16p11.2 deletion diagnostics. The care of patients with this anomaly is based on regular health assessment and adjustment of nervous system development therapy.