Clinical case of differential diagnosis of relapsing oligoarthritis in a child with risk of juvenile idiopathic arthritis

The aim of this clinical case - to suggest the pathogenesis and etiology of relapsing oligoarthritis in the patient.Цель данного клинического наблюдения - проведение дифференциальной диагностики и предположение этиопатогенеза протекающего рецидивирующего олигоартрита у ребенка

Clinical case of cystic fibrosis

A clinical case of cystic fibrosis caused by del F508 mutation in three patients from the same family was analyzed. There was compared a clinical picture, computed tomography data, mucus pharynx sowing and coprograms in three age periods (2-3 years, 3-4 years, 6-7 years).Был проанализирован клинический случай муковисцидоза, вызванного мутацией del F508, у трех пациенток из одной семьи. Проведено сравнение клинической картины, данных компьютерной томографии, посевов слизи зева и копрограмм пациенток в трех возрастных периодах (2-3 г., 3-4 г., 6-7 л.)

Clinical case of cystic fibrosis

A clinical case of cystic fibrosis caused by del F508 mutation in three patients from the same family was analyzed. There was compared a clinical picture, computed tomography data, mucus pharynx sowing and coprograms in three age periods (2-3 years, 3-4 years, 6-7 years).Был проанализирован клинический случай муковисцидоза, вызванного мутацией del F508, у трех пациенток из одной семьи. Проведено сравнение клинической картины, данных компьютерной томографии, посевов слизи зева и копрограмм пациенток в трех возрастных периодах (2-3 г., 3-4 г., 6-7 л.)

Clinical case: glycine encephalopathy

The aim of the study – description of a clinical case of a child diagnosed with glycine encephalopathy.Цель исследования – описать клинический случай ребенка с диагнозом глициновая энцефалопатия

Public knowledge and behaviours relating to antibiotic use in Gulf Cooperation Council countries: A systematic review

© 2018 The Authors The aim of this review was to assess public knowledge and behaviours in relation to antibiotic use in GCC countries. A systematic review was performed using MEDLINE, EMBASE and other relevant databases. Cross-sectional studies published from January 2000 to June 2017 relating to public knowledge and behaviours towards antibiotic use were included. Overall nine studies met the inclusion criteria for this systematic review. Nearly half of general public respondents in the GCC region reported a lack of knowledge about antibiotic use and showed negative attitudes towards antibiotic utilisation. Penicillin was the most frequently misused antibiotic, particularly for self-medication. Most respondents declared that they obtained information on antibiotics from pharmacists. Pharmacies were the major source of antibiotics used for self-medication. A multi-disciplinary approach must be put in place to educate the public on appropriate antibiotic use, to improve policies regarding the rational prescription of antimicrobials and to increase regulation enforcement

BET bromodomains regulate transforming growth factor-beta-induced proliferation and cytokine release in asthmatic airway smooth muscle

Airway smooth muscle (ASM) mass is increased in asthma, and ASM cells from patients with asthma are hyperproliferative and release more IL-6 and CXCL8. The BET (bromo- and extra-terminal) family of proteins (Brd2, Brd3, and Brd4) govern the assembly of histone acetylation-dependent chromatin complexes. We have examined whether they modulate proliferation and cytokine expression in asthmatic ASM cells by studying the effect of BET bromodomain mimics JQ1/SGCBD01 and I-BET762. ASM cells from healthy individuals and nonsevere and severe asthmatics were pretreated with JQ1/SGCBD01 and I-BET762 prior to stimulation with FCS and TGF-β. Proliferation was measured by BrdU incorporation. IL-6 and CXCL8 release was measured by ELISA, and mRNA expression was measured by quantitative RT-PCR. ChIP using a specific anti-Brd4 antibody and PCR primers directed against the transcriptional start site of IL-6 and CXCL8 gene promoters was performed. Neither JQ1/SGCBD01 nor I-BET762 had any effect on ASM cell viability. JQ1/SGCBD01 and I-BET762 inhibited FCS+TGF-β-induced ASM cell proliferation and IL-6 and CXCL8 release in healthy individuals (≥ 30 nm) and in nonsevere and severe asthma patients (≥100 nm), with the latter requiring higher concentrations of these mimics. JQ1/SGCBD01 reduced Brd4 binding to IL8 and IL6 promoters induced by FCS+TGF-β. Mimics of BET bromodomains inhibit aberrant ASM cell proliferation and inflammation with lesser efficiency in those from asthmatic patients. They may be effective in reducing airway remodeling in asthma

A Loss of Function Screen of Identified Genome-Wide Association Study Loci Reveals New Genes Controlling Hematopoiesis

The formation of mature cells by blood stem cells is very well understood at the cellular level and we know many of the key transcription factors that control fate decisions. However, many upstream signalling and downstream effector processes are only partially understood. Genome wide association studies (GWAS) have been particularly useful in providing new directions to dissect these pathways. A GWAS meta-analysis identified 68 genetic loci controlling platelet size and number. Only a quarter of those genes, however, are known regulators of hematopoiesis. To determine function of the remaining genes we performed a medium-throughput genetic screen in zebrafish using antisense morpholino oligonucleotides (MOs) to knock down protein expression, followed by histological analysis of selected genes using a wide panel of different hematopoietic markers. The information generated by the initial knockdown was used to profile phenotypes and to position candidate genes hierarchically in hematopoiesis. Further analysis of brd3a revealed its essential role in differentiation but not maintenance and survival of thrombocytes. Using the from-GWAS-to-function strategy we have not only identified a series of genes that represent novel regulators of thrombopoiesis and hematopoiesis, but this work also represents, to our knowledge, the first example of a functional genetic screening strategy that is a critical step toward obtaining biologically relevant functional data from GWA study for blood cell traits

Selective small molecule induced degradation of the BET bromodomain protein BRD4

The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1. However, the lack of intra-BET selectivity limits the scope of current inhibitors as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We designed Proteolysis Targeted Chimeras (PROTACs) that tether JQ1 to a ligand for the E3 ubiquitin ligase VHL, aimed at triggering the intracellular destruction of BET proteins. Compound MZ1 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 over BRD2 and BRD3. The activity of MZ1 is dependent on binding to VHL but is achieved at a sufficiently low concentration not to induce stabilization of HIF-1α. Gene expression profiles of selected cancer-related genes responsive to JQ1 reveal distinct and more limited transcriptional responses induced by MZ1, consistent with selective suppression of BRD4. Our discovery opens up new opportunities to elucidate the cellular phenotypes and therapeutic implications associated with selective targeting of BRD4

Круп у детей в период пандемии COVID-19

Croup syndrome remains one of the most common diseases in children, while being a life-threatening condition for the patient. Materials and methods. The paper presents the clinical and epidemiological features of croup in 79 children aged 0 months. up to 5 years of age hospitalized during the COVID-19 pandemic from January to September 2022. Results. In the age structure of patients, children of the first year of life predominated. The clinical picture of croup against the background of COVID-19 was usually characterized by an acute onset, febrile fever with the addition of symptoms of stenosing laryngotracheitis on the second and third days from the onset of the disease. The appointment of timely and adequate therapy at all stages of care is the key to a favorable outcome of croup in children.Синдром крупа остается одним из самых распространенных заболеваний у детей, при этом является угрожающим состоянием для жизни пациента. Материалы и методы. В работе представлены клинико-эпидемиологические особенности крупа у 79 детей в возрасте от 0 мес. до 5 лет, госпитализированных в стационар в период пандемии COVID-19 с января по сентябрь 2022 г. Результаты. В возрастной структуре пациентов преобладали дети первого года жизни. Клиническая картина крупа на фоне COVID-19 как правило характеризовалась острым началом, фебрильной лихорадкой с присоединением симптомов стенозирующего ларинготрахеита на второй и третий дни с момента развития заболевания. Назначение своевременной и адекватной терапии на всех этапах оказания помощи является залогом благоприятного исхода крупа у детей