Both denosumab (DMB) and bisphosphonates (BPs), antiresorptive drugs (ARDs) used for the treatment of osteoporosis and oncological disorders, are known for their potential to cause medication-related osteonecrosis of the jaws (MRONJ). Besides ARDs, statins were recently associated with MRONJ development, especially in patients taking higher doses of statins for a longer period of time. Here, we report a case of a female patient with osteoporosis using statins and treated with alendronate for 3 years who rapidly developed MRONJ stage III after only a single low dose of DMB. After partial maxillectomy complete healing was observed without any recurrence. We performed a literature review of cases with MRONJ triggered by a single low dose of DMB, with or without previous application of other ARDs. Only six similar cases of patients who developed MRONJ after a single low dose of DMB following previous BP therapy have been reported so far. Besides these, literature reports one patient who developed MRONJ after a single dose of DMB following romosozumab treatment and five cases developing MRONJ after a single dose of DMB even without any previous ARD treatment. We suggest that before DMB therapy is initiated, all factors predisposing to MRONJ development should be considered.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The antibiotic resistance genes (ARGs) limit the susceptibility of bacteria to antimicrobials, representing a problem of high importance. Current research on the presence of ARGs in microorganisms focuses mainly on humans, livestock, hospitals, or wastewater. However, the spectrum of ARGs in the dust resistome in workplaces and households has gone relatively unexplored. This pilot study aimed to analyze resistome in indoor dust samples from participants' workplaces (a pediatric hospital, a maternity hospital, and a research center) and households and compare two different approaches to the ARGs analysis; high-throughput quantitative PCR (HT-qPCR) and whole metagenome shotgun sequencing (WMGS). In total, 143 ARGs were detected using HT-qPCR, with ARGs associated with the macrolides, lincosamides, and streptogramin B (MLSB) phenotype being the most abundant, followed by MDR (multi-drug resistance) genes, and genes conferring resistance to aminoglycosides. A higher overall relative quantity of ARGs was observed in indoor dust samples from workplaces than from households, with the pediatric hospital being associated with the highest relative quantity of ARGs. WMGS analysis revealed 36 ARGs, of which five were detected by both HT-qPCR and WMGS techniques. Accordingly, the efficacy of the WMGS approach to detect ARGs was lower than that of HT-qPCR. In summary, our pilot data revealed that indoor dust in buildings where people spend most of their time (workplaces, households) can be a significant source of antimicrobial-resistant microorganisms, which may potentially pose a health risk to both humans and animals.

• MeSH
• antibakteriální látky farmakologie   MeSH
• Bacteria genetika   izolace a purifikace   účinky léků   klasifikace   MeSH
• bakteriální geny genetika   MeSH
• bakteriální léková rezistence genetika   MeSH
• charakteristiky rodiny MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• metagenom MeSH
• mikrobiologie vzduchu MeSH
• pilotní projekty MeSH
• prach * analýza   MeSH
• pracoviště * MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• znečištění vzduchu ve vnitřním prostředí MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Mouth breathing (MB), a risk factor of oral dysbiosis and halitosis, is linked with craniofacial anomalies and pediatric obstructive sleep apnea. Here, we aimed to analyze tongue microbiota in children from the perspective of their breathing pattern before/during orthodontic treatment. METHODS: This prospective case-control study included 30 children with orthodontic anomalies, 15 with MB and 15 with nasal breathing (NB), matched by age, sex, and body mass index. All underwent orthodontic examination and sleep apnea monitoring. Tongue swabs were collected before starting (timepoint M0) and approx. six months into the orthodontic therapy (timepoint M6). Oral candidas and bacteriome were analyzed using mass spectrometry technique and 16S rRNA sequencing, respectively. RESULTS: MB was associated with higher apnea-hypopnea index. At M0, oral candidas were equally present in both groups. At M6, Candida sp. were found in six children with MB but in none with NB. No significant differences in bacterial diversity were observed between groups and timepoints. However, presence/relative abundance of genus Solobacterium was higher in children with MB than NB at M0. CONCLUSIONS: Significant links between MB and the presence of genus Solobacterium (M0) as well as Candida sp. (M6) were found in children with orthodontic anomalies, highlighting the risk of halitosis in them.

• MeSH
• dítě MeSH
• dýchání ústy * MeSH
• halitóza mikrobiologie   MeSH
• jazyk * mikrobiologie   MeSH
• lidé MeSH
• mikrobiota * MeSH
• prospektivní studie MeSH
• RNA ribozomální 16S analýza   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Along with individual's genetic predisposition, host microbiome is an important factor in etiopathogenesis of gastroesophageal reflux disease (GERD), increasing significantly risk of developing esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). The project aim is to determine markers at the level of microbiome, host genes and their interactions for earlier diagnosis/prediction of BE and EAC The project includes analyses of (1) metagenome and metatranscriptome at several sites of gastrointestinal tract (GIT) in GERD patients, (2) host exome and transcriptome in esophageal tissue in patients with BE/EAC, and (3) genetic profile of GERD patients. Mutations in patient ́s exome/genome and gene expression levels in esophagus tissue will be correlated with microbiome and its functional activity in the GIT and clinical finding with in vivo endomicroscopy. Based on the obtained data, we will propose modification of the standard care regime for GERD patients to avoid progressive/irreversible changes reducing patients ́ life quality or even threating their lives.

Hostitelský mikrobiom spolu s genetickou predispozicí jedince jsou důležitými faktory v etiopatogenezi refluxní choroby jícnu (GERD), která významně zvyšuje riziko rozvoje ezofagitidy (RE), Barrettova jícnu (BE) a adenokarcinomu ezofagu (EAC). Cílem projektu je determinace markerů na úrovni mikrobiomu, genů hostitele a jejich interakcí pro časnější diagnostiku a predikci rozvoje BE a EAC. Projekt obsahuje 3 části: (1) analýzu metagenomu a metatranskriptomu v několika lokalitách gastrointestinálního traktu (GIT) u pacientů s GERD, (2) analýzu hostitelského exomu a transkriptomu ve tkáni jícnu u pacientů s BE/EAC, a (3) analýzu genetického profilu pacientů s GERD a jeho komplikacemi. Mutace v exomu/genomu pacienta a míra exprese genů ve tkáni jícnu budou korelovány s mikrobiomem a jeho funkční aktivitou v GITu a klinickým nálezem doplněným o in vivo endomikroskopii. Na základě získaných dat se pokusíme navrhnout modifikaci standardního režimu péče o pacienty s GERD s cílem předejít pokročilým a ireverzibilním změnám snižujícím kvalitu života pacientů, resp. ohrožujících je na životě.

• Klíčová slova
• sekvenování nové generace, mikrobiom, microbiome, Genetická predispozice, Genetic predisposition, In vivo diagnostika, refluxní choroba jícnu, Barrettův jícen, adenokarcinom jícnu, in vitro diagnostika, Barrett's esophagus, in vitro diagnostics, Next-generation sequencing, Esophageal adenocarcinoma, in vivo diagnostics, metatranskriptom, metatranscriptome, esophageal reflux disease,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Infections affecting the root canal of the tooth are the most common cause of apical periodontitis (AP). Chronic inflammation in the periodontium may lead to the development of a radicular cyst (RC), a type of inflammatory odontogenic cyst (OC). OC of developmental origin also includes dentigerous cysts (DC) and odontogenic keratocysts (OKC). Correct classification of OCs reflecting their etiopathogenesis including genetic factors is crucial for choosing an optimum therapy and patient management. The aim of the project is to identify risk factors of OC development and improve their diagnosis. The project includes study of microbiome present in the root canal, genetic association studies focused on patients ́immune profiling and influence of genes envolved in odontogenesis, comparative studies of gene expression profiles in various types of odontogenic cysts, and study of selected molecular pathways in OC pathogenesis in an animal model. Based on the obtained results we will propose a panel of markers for prediction of OC development and differential diagnosis of OC types.

Infekce postihující kořenový kanálek zubu je nejčastější příčinou vzniku apikální periodontitidy (AP). Chronický zánět v periodonciu může vést k rozvoji radikulární cysty (RC), která patří k zánětlivým odontogenním cystám (OC). Další skupinu tvoří OC vývojové, k nimž se mimojiné řadí cysta folikulární (FC) a odontogenní keratocysta (OKC). Pro optimální volbu terapie a manažment pacientů je klasifikace OC, která reflektuje jejich etiopatogenezi a zahrnuje genetické faktory, zásadní. Cílem projektu je determinace rizikových faktorů rozvoje OC a zlepšení jejich diagnostiky. Projekt zahrnuje studii mikrobiomu kořenového kanálku zubu a OC zánětlivého původu, genetické asociační studie se zaměřením na imunitní profil pacientů a geny zapojené do odontogeneze, komparativní studie expresních profilů genů v různých typech OC, a studie vybraných molekulárních drah v patogenezi OC na animálním modelu. Na základě získaných výsledků se pokusíme navrhnout panel markerů pro predikci vzniku OC a jejich diferenciální diagnostiku.

• Klíčová slova
• Genetická predispozice, Genetic predisposition, sequencing, Nanočástice, imunogenetika, nanoparticle, sekvenování, immunogenetics, apical periodontitis, orální mikrobiom, oral microbiome, SHH signalizace, in vivo animální model, odontogenní cysta, apikální periodontitida, SHH signaling, in vivo animal model, odontogenic cyst,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

This study aimed to create a Czech questionnaire for pediatric obstructive sleep apnea (POSA) risk screening, a first of its kind in the Czech Republic, where options for child polysomnography are limited. Compiling items from established English questionnaires and supplementing them with additional items, we designed the first version of the Czech questionnaire and tested it in a pilot study with parents of 30 children. After pilot feedback, a revised version with dichotomous and 5-item Likert scale questions was tested on 71 children's parents. All children (7-12 years old) underwent a home sleep apnea test to record their apnea-hypopnea index (AHI). The second (40-item) version showed high reliability (93%), with 17 items identified as the most significant. Findings from the final 17-item SEN CZ questionnaire correlated positively with AHI (p < 0.001), demonstrating 84% sensitivity, 86% specificity, and 93% reliability. Three factors, namely breathing problems, inattention, and hyperactivity (characterized by multiple items), were identified to form a higher-order factor of POSA risk, which was further supported by the correlations of their total scores with AHI (p < 0.001). The resulting SEN CZ questionnaire can serve as a tool for POSA risk screening in the Czech Republic without the need to involve medical professionals.

• MeSH
• dítě MeSH
• lidé MeSH
• obstrukční spánková apnoe * diagnóza   epidemiologie   MeSH
• pilotní projekty MeSH
• plošný screening metody   MeSH
• polysomnografie metody   MeSH
• průzkumy a dotazníky MeSH
• reprodukovatelnost výsledků MeSH
• rizikové faktory MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Intrapartum antibiotic prophylaxis (IAP) is commonly used during C-section delivery and in Group B Streptococcus-positive women before vaginal delivery. Here, we primarily aimed to investigate the effect of IAP on the neonatal oral and fecal bacteriomes in the first week of life. In this preliminary study, maternal and neonatal oral swabs and neonatal fecal (meconium and transitional stool) swabs were selected from a pool of samples from healthy mother-neonate pairs participating in the pilot phase of CELSPAC: TNG during their hospital stay. The DNA was extracted and bacteriome profiles were determined by 16S rRNA amplicon sequencing (Illumina). In the final dataset, 33 mother-neonate pairs were exposed to antibiotics during C-section or vaginal delivery (cases; +IAP) and the vaginal delivery without IAP (controls, -IAP) took place in 33 mother-neonate pairs. Differences in alpha diversity (Shannon index, p=0.01) and bacterial composition (PERMANOVA, p<0.05) between the +IAP and -IAP groups were detected only in neonatal oral samples collected ≤48 h after birth. No significant differences between meconium bacteriomes of the +IAP and -IAP groups were observed (p>0.05). However, the IAP was associated with decreased alpha diversity (number of amplicon sequence variants, p<0.001), decreased relative abundances of the genera Bacteroides and Bifidobacterium, and increased relative abundances of genera Enterococcus and Rothia (q<0.01 for all of them) in transitional stool samples. The findings of this study suggest that exposure to IAP may significantly influence the early development of the neonatal oral and gut microbiomes. IAP affected the neonatal oral bacteriome in the first two days after birth as well as the neonatal fecal bacteriome in transitional stool samples. In addition, it highlights the necessity for further investigation into the potential long-term health impacts on children.

• MeSH
• antibakteriální látky * aplikace a dávkování   MeSH
• antibiotická profylaxe * metody   MeSH
• Bacteria genetika   klasifikace   izolace a purifikace   účinky léků   MeSH
• císařský řez MeSH
• dospělí MeSH
• feces * mikrobiologie   MeSH
• lidé MeSH
• mekonium mikrobiologie   MeSH
• novorozenec MeSH
• RNA ribozomální 16S genetika   MeSH
• střevní mikroflóra účinky léků   MeSH
• těhotenství MeSH
• ústa * mikrobiologie   MeSH
• vedení porodu MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Specific toxic compounds, such as polycyclic aromatic hydrocarbons (PAHs) and their metabolites, may affect the inhalation injury (INHI) grade, patients' status, and prognosis for recovery. This pilot prospective study aimed to: i) evaluate the suitability of bronchoalveolar lavage (BAL) for determination of PAHs in the LRT and of urine for determination of hydroxylated metabolites (OH-PAHs) in patients with INHI, ii) describe the dynamic changes in the levels of these toxic compounds, and iii) correlate these findings with clinical variables of the patients with INHI. METHODS: The BAL and urine samples from 10 patients with INHI were obtained on Days 1, 3, 5, 7, and 14 of hospitalization, if possible, and PAHs (BAL) and OH-PAHs (urine) were analyzed using chromatographic methods (GC-MS and HPLC). RESULTS: Concentrations of analyzed PAHs were in most cases and time points below the limit of quantification in BAL samples. Nine OH-PAHs were detected in the urine samples; however, their concentrations sharply decreased within the first three days of the hospitalization. On Day 14, the total amount of OH-PAHs in urine was higher in surviving patients with High-grade INHI (≥3) than in those with Low-grade INHI (<3, p = 0.032). Finally, a significant correlation between certain OH-PAHs and clinical variables (AST/ALT, TBSA, ABSI) from Day 1 of the hospitalization was observed (p<0.05). CONCLUSIONS: BAL samples are not suitable for the analysis of PAHs. However, the OH-PAHs levels in urine can be measured reliably and were correlated with several clinical variables. Moreover, High-grade INHI was associated with higher total concentrations of OH-PAHs in urine.

• MeSH
• bronchoalveolární lavážní tekutina * chemie   MeSH
• dospělí MeSH
• hospitalizace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• polycyklické aromatické uhlovodíky * moč   analýza   MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Patients with burn injury and inhalation injury are highly susceptible to infectious complications, including opportunistic pathogens, due to the loss of skin cover and mucosal damage of respiratory tract as well as the disruption of homeostasis. This case report, a 34-year-old man suffered critical burns, provides the first literature description of triple-impact immunoparalysis (critical burns, inhalation injury, and SARS-CoV-2 infection), leading to a lethal multifocal infection caused by several fungi including very rare environmental representatives Metschnikowia pulcherrima and Wickerhamomyces anomalus. The co-infection by these common environmental yeasts in a human is unique and has not yet been described in the literature. Importantly, our patient developed refractory septic shock and died despite targeted antifungal therapy including the most potent current antifungal agent-isavuconazole. It can be assumed that besides immunoparalysis, effectiveness of therapy by isavuconazole was impaired by the large distribution volume in this case. As this is a common situation in intensive care patients, routine monitoring of plasmatic concentration of isavuconazole can be helpful in personalization of the treatment and dose optimization. Whatmore, many fungal species often remain underdiagnosed during infectious complications, which could be prevented by implementation of new methods, such as next-generation sequencing, into clinical practice.

• MeSH
• antifungální látky * terapeutické užití   MeSH
• COVID-19 * imunologie   komplikace   MeSH
• dospělí MeSH
• fatální výsledek MeSH
• koinfekce mikrobiologie   farmakoterapie   imunologie   MeSH
• lidé MeSH
• mykózy farmakoterapie   mikrobiologie   imunologie   diagnóza   MeSH
• nitrily terapeutické užití   MeSH
• popálení komplikace   mikrobiologie   MeSH
• pyridiny terapeutické užití   MeSH
• Saccharomycetales genetika   účinky léků   imunologie   MeSH
• SARS-CoV-2 imunologie   MeSH
• sepse farmakoterapie   mikrobiologie   imunologie   MeSH
• triazoly terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

OBJECTIVES: Dental caries is a widespread multifactorial disease, caused by the demineralization of hard dental tissues. Susceptibility to dental caries is partially genetically conditioned; this study was aimed at finding an association of selected single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in amelogenesis with this disease in children. MATERIALS AND METHODS: In this case-control study, 15 SNPs in ALOX15, AMBN, AMELX, KLK4, TFIP11, and TUFT1 genes were analyzed in 150 children with primary dentition and 611 children with permanent teeth with/without dental caries from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) cohort. RESULTS: Dental caries in primary dentition was associated with SNPs in AMELX (rs17878486) and KLK4 (rs198968, rs2242670), and dental caries in permanent dentition with SNPs in AMELX (rs17878486) and KLK4 (rs2235091, rs2242670, rs2978642), (p ≤ 0.05). No significant differences between cases and controls were observed in the allele or genotype frequencies of any of the selected SNPs in ALOX15, AMBN, TFIP11, and TUFT1 genes (p > 0.05). Some KLK4 haplotypes were associated with dental caries in permanent dentition (p ≤ 0.05). CONCLUSIONS: Based on this study, we found that although the SNPs in AMELX and KLK4 are localized in intronic regions and their functional significance has not yet been determined, they are associated with susceptibility to dental caries in children. CLINICAL RELEVANCE: AMELX and KLK4 variants could be considered in the risk assessment of dental caries, especially in permanent dentition, in the European Caucasian population.

• MeSH
• amelogeneze * genetika   MeSH
• amelogenin genetika   MeSH
• dítě MeSH
• lidé MeSH
• longitudinální studie MeSH
• studie případů a kontrol MeSH
• zubní kaz * genetika   epidemiologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH