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Gyermekkori genetikai rendellenességek diagnosztikája újgenerációs szekvenálással
Diagnosis of genetic disorders in childhood with next-generation sequencing
Az újgenerációs szekvenáláson (NGS) alapuló diagnosztika legnagyobb előnye, hogy nagyszámú gén párhuzamos szekvenálása révén a genetikai rendellenességek kiterjedt repertoárját képes egyetlen vizsgálattal lefedni. Az analízis viszonylag kisebb költsége és az adatmennyiség kezelhetőbb mennyisége folytán a célzott génpanelek használata, illetve a teljesexom-szekvenálás (WES) a leginkább elérhető NGS-alapú módszer. Összefoglalónkban az NGS létjogosultságát vizsgáljuk gyermekkori genetikai rendellenességek diagnosztikájában. Áttekintjük az öröklött anyagcserezavarok, daganatos megbetegedések és egyéb gyermekkori genetikai rendellenességek NGS-alapú diagnosztikájában fontos szerepet játszó géneket. A kora gyermekkori rendellenességek NGS-alapú diagnosztikájának rutinszerű használata előtt számos technikai és klinikai kérdés vár még megválaszolásra. Jelenleg a legnagyobb kihívást a ritka genetikai variánsok értelmezése és a mutációk patogenitásának igazolása jelenti. Orv Hetil. 2022; 163(51): 2027–2040.
Personal choice is a nuanced concept – Lessons learned from the gambling field
Commentary on: Problematic risk-taking involving emerging technologies: A Stakeholder framework to minimize harms (Swanton et al., 2019)
Swanton, Blaszczynski, Forlini, Starcevic, and Gainsbury (2019) propose a thoughtful framework for minimizing the personal harm that is potentially associated with new technologies. Broadly defined these technologies and behaviors include online
A new digital Cobalt-60 combined stereotactic radiotherapy and radiosurgery system, termed as the GyroKnife, was developed in Shanghai, China in 2004. The equipment integrates advantages of previous generations of gamma radiosurgery techniques and linear accelerators. The technology has the capacity for non-invasive whole-body stereotactic fractionated radiotherapy and single high-dose radiosurgery as well. Using a triple focussing method, high isocenter accuracy (0.5~1.0 mm) and minimal skin (550:1) or normal tissue irradiation dose were achieved with 4 various sizes of collimator sets (5, 15, 25, 50 mm). The first GyroKnife Center in Kang Da Hospital, Xiang Fan, China, has already treated 100 cases with different tumours in the brain and body since November 2006. The technical details of the system will be presented, and the preliminary clinical results will also be discussed.
Abstract
In this study, the prevalence of Avian orthoavulavirus-1 (AOAV-1) (also commonly known as Newcastle disease virus) was investigated in caged birds kept in bird markets in the Lahore district of Pakistan. A total of 354 swab samples were obtained from 14 different species of clinically healthy birds. The overall virus prevalence was 12.7% in 9 out of the 14 species. Phylogenetic analysis of the complete fusion protein (F) gene showed that 23 isolates from different avian species belonged to sub-genotype VII.2 while three isolates of pigeon origin clustered with sub-genotype XXI.1.2. The VII.2 viruses isolated had a high nucleotide identity to viruses repeatedly isolated from poultry in Pakistan from 2011 to 2018. To date, sub-genotype XXI.1.2 viruses have only been identified in Pakistan. These findings suggest that the Newcastle disease (ND) outbreaks occurring in Pakistan involve multiple hosts and environments. The study emphasises the importance of continuing to monitor multiple avian species for the presence of AOAV-1s and implementing effective ND control strategies.
Abstract
This study aimed to evaluate the routine identification tools available in Lebanon for differentiation of Escherichia coli and Shigella spp. The identification of 43 isolates defined as Shigella spp. by Api 20E was accessed using MALDI-TOF, serological testing, duplex PCR targeting ipaH (present in Shigella spp. and enteroinvasive E. coli “EIEC”) and lacY (found in E. coli including EIEC but not Shigella spp.) as well as gyrB gene sequencing. Antibiotic susceptibility was investigated as well as Shiga-toxin production. All isolates were identified as E. coli by MALDI-TOF while the PCR showed a disparate group of 26 EIEC, 11 Shigella spp., 5 E. coli and 1 inactive E. coli. However, the sequencing of gyrB gene, which was recently described as a suitable marker for distinguishing E. coli and Shigella spp., identified all isolates as E. coli. Antibiotic resistance was noticeable against ß-lactams, rifampicin, trimethoprim-sulfamethoxazole, gentamicin, and ciprofloxacin. The most common variants of beta-lactamase genes were bla TEM-1, bla CTX-M-15, and bla CTX-M-3. A great discordance between the used methods in identification was revealed herein. An accurate identification technique able to distinguish E. coli from Shigella spp. in routine laboratories is a pressing need in order to select the appropriate treatment and assess the epidemiology of these bacteria.
Abstract
The commensal microflora collection known as microbiota has an essential role in maintaining the host's physiological homeostasis. The microbiota has a vital role in induction and regulation of local and systemic immune responses. On the other hand, the immune system involves maintaining microbiota compositions. Optimal microbiota-immune system cross-talk is essential for protective responses to pathogens and immune tolerance to self and harmless environmental antigens. Any change in this symbiotic relationship may cause susceptibility to diseases. The association of various cancers and auto-immune diseases with microbiota has been proven. Here we review the interaction of immune responses to gut microbiota, focusing on innate and adaptive immune system and disease susceptibility.
Abstract
Efflux pumps play an important role in the emergence of antibiotic-resistant Pseudomonas aeruginosa strains. The present study aimed to assess the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps in carbapenem-resistant and multidrug-resistant (MDR) P. aeruginosa strains isolated from clinical specimens between June 2019 and January 2022 in Ardabil city. The presence of efflux pump-encoding genes, i.e. mexA, mexC, mexE, and mexY, was assessed using the polymerase chain reaction (PCR) technique in 48 carbapenem-resistant and MDR P. aeruginosa strains. Real-time reverse transcription PCR was employed to evaluate the expression levels of mexA, mexC, mexE, and mexY genes. All 48 carbapenem-resistant and MDR P. aeruginosa strains harbored efflux pump-encoding genes including mexA, mexC, mexE, and mexY according to the PCR results. Overexpression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM efflux pumps was detected in 75% (n = 36), 83.3% (n = 40), 10.4% (n = 5) and 41.6% (n = 20) of the clinical isolates of P. aeruginosa, respectively. This study revealed that the presence and overexpression of efflux pumps are associated with the emergence of carbapenem-resistant and MDR P. aeruginosa strains. Therefore, research on efflux pump inhibitors of P. aeruginosa will be a worthwhile endeavor to increase the clinical efficiency of available antibiotics and prevent ensuing treatment failure.
First-line antihypertensive treatment’s drugs have to be able to decrease the cardiovascular morbidity and mortality. This kind of efficacy of thiazide-type diuretics has been published earlier in several studies. The efficacy of indapamide was investigated in several studies, but there is no analysis which is including all of the indapamide-studies. Objective: We conducted a meta-analysis of all relevant randomized-controlled-trials with indapamide. Efficacy of indapamide was analyzed in different cardiovascular and safety outcomes. Methods: We searched the MEDLINE database 1995–2006 for indapamide-trials. Only double-blind, parallel-group design trials were involved. Both the fixed effect model and the random effect model were used for data synthesis, results were probed with Mantel–Hanzel test and inverse variance test. Results: Data were combined from 9 trials that included 10,108 patients. Indapamide treatment of 48 patients with a history of stroke prevents one stroke (NNT = 47.8 95% CI: 29.6–126.6). Data from 5 trials including 7,085 patients show that indapamide is superior to placebo in reducing blood pressure, the differences are: 7.28 mm Hg (95% CI: 6.37–8.19) in systolic blood pressure and 3.50 mm Hg (95% CI: 2.99–4.01) in diastolic blood pressure. Data from 5 trials including 2,856 patients show that indapamide is superior to active controls in reducing systolic blood pressure, the difference is significant: 1.30 mm Hg (95% CI: 0.28–2.31). The difference in diastolic blood pressure was not significant. Data of 505 patients show that indapamide reduced left ventricular mass index significantly more than enalapril 20 mg, the difference is 6.50 g/m 2 (95% CI: 0.81–12.19). Data of 6,206 patients show that the frequency of adverse drug reaction is similar in the indapamide and placebo groups (RR = 0.97 95% CI: 0.76–1.22). Conclusions: Indapamide is efficacious in the prevention of further stroke, reduces effectively the blood pressure and the left ventricular mass index. Indapamide treatment is well tolerated.
Abstract
This study was conducted to evaluate the pharmacokinetics of cefquinome in camel calves after a single intramuscular injection in a dose of 2 mg/kg body weight (kg b. w.). Cefquinome concentrations were measured by ultra-high performance liquid chromatography–mass spectrometry (UPLC-MS/MS). A non-compartmental pharmacokinetic model was used to fit the time–concentration curve and estimate the pharmacokinetic parameters. The peak serum concentration (Cmax) was 28.4 μg/mL at the time of maximum concentration (Tmax) of 25 min. The elimination half-life (t1/2) was 17.4 h. The area under the concentration–time curve (AUC0–∞) was 103.7 μg/ml−1h and the mean residence time (MRT0–∞) was 21.3 h. In comparison with other animal species, the pharmacokinetics of cefquinome in Arabian camel calves showed faster absorption from the site of injection and slower elimination. Since cefquinome, as other beta-lactams, is a time-dependent antimicrobial agent, a single dose of 2 mg/kg b. w. might be sufficient against the most sensitive organisms in camel calves owing to its prolonged elimination phase. However, dose readjustment is required for cases needing concentrations above 2 µg/mL for 12 h or above 1 µg/mL for 24 h.
