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

The increase in resistance of microorganisms is a current worldwide problem, not only in hospitalized patients, but also in patients treated on an outpatient basis. Therefore, it is necessary to look for innovative therapeutic alternatives that could reduce antibiotic selection pressure on given microorganisms and increase chances of their eradication. Currently, at the forefront of interest in wound management and local application are natural products. Based on our preliminary experiments, one of the most promising materials that meets modern requirements for temporal dressing (epithelialization support, antimicrobial activity, exudate absorption etc.) is undoubtedly Gum Karaya (GK). In the project, we will focus on a modern approach to wound healing by using GK in different forms (hydrogel, porous film, fiber dressing) to control antibacterial biogenic system release (bacteriophages, antibacterial proteins and nanoparticles) targeted at multidrug resistant bacterial strains. Dressing efficacy against bacteria will be evaluated preclinically on pig animal model.

Nárůst rezistence mikroorganismů je současný celosvětový problém nejen u hospitalizovaných pacientů, ale také u pacientů léčených ambulantně. Je proto nutné hledat terapeutické alternativy, které by mohly snížit selekční tlak antibiotik na dané mikroorganismy a zvýšily by šanci na jejich eradikaci. V současné době se dostávají do popředí zájmu ve wound managementu i v lokálním podání přírodní produkty. Jedním z velmi nadějných materiálů je přírodní pryskyřice Gum Karaya (GK), která na základě našich předběžných výsledků splňuje současné požadavky na dočasný kryt ran (podpora epitelizace, antimikrobiální aktivita, absorpce exudátu aj.). V projektu se zaměříme na moderní přístup k hojení infikované rány, kdy využijeme pryskyřici GK v různých formách (hydrogel, porézní film a vlákenný kryt) na řízené uvolňování antibakteriálních biogenních systémů (bakteriofágů, antibakteriálních proteinů a nanočástic) zaměřených proti multirezistentním kmenům bakterií. Účinnost krytů vůči bakteriím bude testována preklinicky na animálním modelu prasete.

• Klíčová slova
• Bakteriofágy, Bacteriophages, antimikrobiální peptidy, antimicrobial peptides, fágy, phages, Biopolymerní hydrogel, Multirezistentní kmeny bakterií, Komplikovaná infekce kůže a měkkých tkání, Nanočástice selenu, Biopolymer hyrogel, Multidrug-resistant bacterial strains, Complicated skin and soft tissue infection, Selenium nanoparticles,

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

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a common treatment for intermediate and late stages of Parkinson’s disease (PD). The development of PD is associated with the progression of several non-motor symptoms that may predominate the clinical picture and which may substantially worsen in the course of STN DBS. Among the ‘hard’ criteria that exclude patients from the DBS program are atypical parkinsonian syndromes, dementia, actual depression, recurrent psychotic conditions, and postural instability with gait disorder despite optimal dopaminergic therapy. On the other hand, ‘soft’ exclusion criteria are associated with axial motor symptoms, higher biological age, the occurrence of mild cognitive impairment, a history of sporadic pre-psychotic symptoms, or a preceding anxiety-depressive episode. The aim of this project is to challenge the ‘soft’ criteria and to establish the importance of individual indicators in predicting the future of a STN DBS outcome as well as to define new additional criteria based on multi-modal preoperative testing.

Hluboká mozková stimulace (DBS) u Parkinsonovy nemoci (PN) je standardní léčebnou metodou pozdního a intermediálního stádia. Vývoj PN je spojen s rozvojem řady non-motorických symptomů, které v klinickém obraze mnohdy dominují, a které se mohou během DBS STN významně zhoršit. Mezi „tvrdá“ kritéria, na základě kterých bývá pacient z indikačního procesu DBS obvykle vyloučen, jsou projevy atypických parkinsonských syndromů, symptomy u PN s klinickým obrazem demence, floridní deprese, opakovanými psychotickými stavy, posturální nestabilitou nebo poruchou chůze a to i přes optimálně vedenou dopaminergní léčbu. „Měkká“ vylučovací kritéria jsou spojena s vyšším biologickým věkem, výskytem mírné kognitivní poruchy, anamnézou sporadických pre-psychotických symptomů či předchozí úzkostně-depresivní epizodou. Záměrem předkládaného projektu je snaha prověřit stávající měkká indikační kritéria s cílem stanovit důležitost jednotlivých ukazatelů v predikci budoucího úspěchu DBS STN současně se snahou doplnit je o kritéria nová, opřená o multimodální předoperační nálezy.

• Klíčová slova
• biomarkery, biomarkers, Parkinsonova nemoc, Parkinson Disease, mírná kognitivní porucha, mild cognitive impairment, řeč, subthalamic nucleus, hluboká mozková stimulace, deep brain stimulation, Oční pohyby, Eye movements, subtalamické jádro, resting state fMRI, mikroregistrace, non-motorické příznaky, axiální příznaky, DBS, resting state fMRI, speech production, microrecording, non-motor symptoms, axial symptoms, DBS,

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

Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.

• MeSH
• hluboká mozková stimulace * metody   MeSH
• kognice fyziologie   MeSH
• kognitivní dysfunkce * etiologie   terapie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuropsychologické testy MeSH
• nucleus subthalamicus * MeSH
• Parkinsonova nemoc * terapie   patofyziologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Pseudomonas aeruginosa poses a significant threat to both immunocompetent and immunocompromised individuals, often resulting in life-threatening infections. With increasing antimicrobial resistance, novel therapeutic strategies are urgently needed. Although animal models are crucial for preclinical studies, limited data are available for porcine models, more specifically for P. aeruginosa complicated skin and soft tissue infections (cSSTIs). This study presents a novel porcine model inducing and sustaining cSSTI for 14 days. Six pigs (120 wounds) were used for the development of infections, and within this group, two pigs (40 wounds) were used to evaluate the progression of the cSSTI infection. The model demonstrated bacterial loads of more than 107 CFU/gram of tissue or higher. The cSSTI fully developed within three days and remained well above these levels until day 14 post-infection. Due to the immunocompetence of this model, all the immunological processes associated with the response to the presence of infection and the wound healing process are preserved.

BACKGROUND AND OBJECTIVES: The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients. METHODS: Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2. RESULTS: PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups. CONCLUSIONS: Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.

• MeSH
• hluboká mozková stimulace * škodlivé účinky   MeSH
• kognitivní dysfunkce * etiologie   diagnostické zobrazování   patofyziologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• neuropsychologické testy MeSH
• nucleus subthalamicus * diagnostické zobrazování   MeSH
• Parkinsonova nemoc * terapie   diagnostické zobrazování   patologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Parkinson's disease (PD), even though generally perceived as a dominantly motor disorder, is associated with a wide range of non-motor symptoms, including mixed anxiety-depressive disorder (MADD). OBJECTIVES: The aim of the presented study was to determine whether deep brain stimulation (DBS) of the subthalamic nucleus (STN) brings the functional characteristics of non-motor networks closer to the condition detected in healthy population and whether pre-DBS presence of MADD in PD patients was associated with different reaction to this therapeutic modality. METHODS: Resting-state fMRI signature elicited by STN DBS activation and deactivation in 81 PD patients was compared against healthy controls, with the focus on measures of efficiency of information processing and localised subnetwork differences. RESULTS: While all the MRI metrics showed statistically significant differences between PD patients in DBS OFF condition and healthy controls, none were detected in such a comparison against DBS ON condition. Furthermore, in the post-DBS evaluation, PD patients with MADD in the pre-DBS stage showed no differences in depression scales compared to pre-DBS psychiatrically intact PD patients, but still exhibited lower DBS-related connectivity in a subnetwork encompassing anterior and posterior cingulate, dorsolateral prefrontal and medial temporal cortices. CONCLUSIONS: STN DBS improved all the metrics of interest towards the healthy state, normalising the resting-state MRI signature of PD. Furthermore, pre-DBS presence of MADD, even though clinically silent at post-DBS MRI acquisition, was associated with lower DBS effect in areas highly relevant for depression. This finding points to a possibly latent nature of post-DBS MADD, calling for caution in further follow-up of these patients.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

• MeSH
• antiflogistika terapeutické užití   farmakologie   MeSH
• chlorhexidin terapeutické užití   farmakologie   analogy a deriváty   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• faktor 2 související s NF-E2 MeSH
• fibroblasty * účinky léků   MeSH
• gingiva * účinky léků   MeSH
• gingivitida * farmakoterapie   MeSH
• hemoxygenasa-1 MeSH
• interleukin-6 analýza   MeSH
• interleukin-8 účinky léků   MeSH
• kanabidiol * farmakologie   terapeutické užití   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• parodontitida farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Léčba infekčních onemocnění kůže a měkkých tkání je každodenní praxí lékařů chirurgických oborů, a i přes široké terapeutické možnosti stále představuje značné riziko morbidity i mortality, zejména u těžkých stavů spojených s nekrotizujícími infekcemi. Výskyt patogenních kmenů s rezistencí k antibiotické terapii je i u těchto onemocnění stoupajícím problémem, který vede ke snaze hledat jiné terapeutické možnosti. Jednou ze slibných variant může být i fágová terapie, která právě díky výskytu antibiotických rezistencí zažívá renesanci na poli výzkumu a má potenciál zaujmout místo i v klinické praxi.

Therapy of infectious diseases of skin and soft tissue is a daily part of clinical practice at surgical departments. Despite a wide spectrum of antimicrobial therapeuticals, it still remains a significant morbidity and mortality, especially in the serious cases connected with necrotizing infection. Occurrence of the multiresistant variant of the pathogen is an increasing problem leading to the effort to find other effective therapeutic possibilities. A phage therapy appears to be one of the promising variants with a potential to become a part of common clinical practice.

• MeSH
• bakteriofágy MeSH
• fágová terapie MeSH
• infekce měkkých tkání * terapie   MeSH
• infekční nemoci kůže * terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

INTRODUCTION: Staphylococcus capitis naturally colonizes the human skin but as an opportunistic pathogen, it can also cause biofilm-associated infections and bloodstream infections in newborns. Previously, we found that two strains from the subspecies S. capitis subsp. capitis produce yellow carotenoids despite the initial species description, reporting this subspecies as non-pigmented. In Staphylococcus aureus, the golden pigment staphyloxanthin is an important virulence factor, protecting cells against reactive oxygen species and modulating membrane fluidity. METHODS: In this study, we used two pigmented (DSM 111179 and DSM 113836) and two non-pigmented S. capitis subsp. capitis strains (DSM 20326T and DSM 31028) to identify the pigment, determine conditions under which pigment-production occurs and investigate whether pigmented strains show increased resistance to ROS and temperature stress. RESULTS: We found that the non-pigmented strains remained colorless regardless of the type of medium, whereas intensity of pigmentation in the two pigmented strains increased under low nutrient conditions and with longer incubation times. We were able to detect and identify staphyloxanthin and its derivates in the two pigmented strains but found that methanol cell extracts from all four strains showed ROS scavenging activity regardless of staphyloxanthin production. Increased survival to cold temperatures (-20°C) was detected in the two pigmented strains only after long-term storage compared to the non-pigmented strains. CONCLUSION: The identification of staphyloxanthin in S. capitis is of clinical relevance and could be used, in the same way as in S. aureus, as a possible target for anti-virulence drug design.

• Publikační typ
• časopisecké články MeSH