INTRODUCTION: Impaired copy of intersecting pentagons from the Mini-Mental State Examination (MMSE), has been used to assess dementia in Parkinson's disease (PD). We used a digitizing tablet during the pentagon copying test (PCT) as a potential tool for evaluating early cognitive deficits in PD without major cognitive impairment. We also aimed to uncover the neural correlates of the identified parameters using whole-brain magnetic resonance imaging (MRI). METHODS: We enrolled 27 patients with PD without major cognitive impairment and 25 age-matched healthy controls (HC). We focused on drawing parameters using a digitizing tablet. Parameters with between-group differences were correlated with cognitive outcomes and were used as covariates in the whole-brain voxel-wise analysis using voxel-based morphometry; familywise error (FWE) threshold p < 0.001. RESULTS: PD patients differed from HC in attention domain z-scores (p < 0.0001). In terms of tablet parameters, the groups differed in Shannon entropy (horizontal in-air, p = 0.003), which quantifies the movements between two strokes. In PD, a correlation was found between the median of Shannon entropy (horizontal in-air) and attention z-scores (R = -0.55, p = 0.006). The VBM revealed an association between our drawing parameter of interest and gray matter (GM) volume variability in the right superior parietal lobe (SPL). CONCLUSION: Using a digitizing tablet during the PCT, we identified a novel entropy-based parameter that differed between the nondemented PD and HC groups. This in-air parameter correlated with the level of attention and was linked to GM volume variability of the region engaged in spatial attention.
- MeSH
- entropie MeSH
- kognitivní dysfunkce * MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- neuropsychologické testy MeSH
- Parkinsonova nemoc * komplikace diagnostické zobrazování psychologie MeSH
- šedá hmota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIMS: The aim of this study was to answer the question whether our newly developed injectable biodegradable "self-setting" polymer-composite as a bone adhesive is a good "bone-glue" candidate to efficiently fix comminuted fractures of pig femoral bones used as an ex-vivo experimental model. METHODS: Mechanical properties of adhesive prepared from α-tricalcium phosphate (TCP) powder and thermogelling copolymer were optimized by selecting the appropriate composition with adhesion enhancers based on dopamine and sodium iodinate. Setting time and injectability were controlled by rheology. Ex-vivo experiments of fixed pig bones were provided in terms of either the three-point bending test of bending wedge type fractured pig femurs (with LCP) or the axial compression test of 45° oblique fractured femurs (without LCP) in physiological saline solution at 37 °C. Fractured bones treated with optimized adhesive before and after bending tests were imaged by X-ray microtomography (μCT). RESULTS: Based on the rheological measurement, the adhesive modified with both dopamine and sodium iodinate exhibited optimal thixotropic properties required for injection via thin 22 G needle. This optimal adhesive composition showed an 8 min lag phase (processing time) followed by fast increase in storage modulus at 37 °C up to 1 GPa within 110 min. Self-setting of dopamine/iodinate modified adhesive was completed in 48 h exhibiting the maximum strength at compression of 7.98 MPa ± 1.39 MPa. Whereas unmodified adhesive failed in glue-to-bone adhesion, dopamine and dopamine/iodinate modified adhesive used for 45° oblique fracture fixation showed good and similar strength at compression (3.05 and 2.79 MPa, respectively). However, significantly higher elasticity of about 250% exhibited adhesive with iodinate enhancer. Moreover, mechanical properties of B2 fractures fixed with both LCP and dopamine/iodinate adhesive were approaching closely to the properties of original bone. Excellent adhesion between the adhesive and the bone fragments was proved by μCT. CONCLUSION: The polymer-composite bone adhesive modified with dopamine/iodinate exhibited very good fixation ability of femoral artificial comminuted fractures in an experimental model.
- MeSH
- biomechanika MeSH
- diafýzy MeSH
- femur diagnostické zobrazování MeSH
- fixace fraktur MeSH
- fraktury femuru * diagnostické zobrazování MeSH
- kostní cementy * MeSH
- kostní destičky MeSH
- prasata MeSH
- vnitřní fixace fraktury MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Platelets (PLTs) stored at 20-24 °C have a short shelf life of only 5 days, which can result in their restricted availability. PLT cryopreservation extends the shelf life to 2 years. METHODS: We implemented a method of PLT freezing at -80 °C in 5-6% dimethyl sulfoxide. Buffy-coat-derived leucodepleted fresh PLTs blood group O (FP) were used for cryopreservation. Cryopreserved pooled leucodepleted PLTs (CPP) were thawed at 37 °C, reconstituted in PLT additive solution SSP + and compared to FP regarding PLT content, PLT concentration, pH, volume, PLT loss, anti-A/B antibody titre, total protein, plasma content, and PLT swirling. Clot properties were evaluated via rotational thromboelastometry. PLT microparticle number and surface receptor phenotype were assessed via flow cytometry. RESULTS: CPP met the required quality parameters. The mean freeze-thaw PLT loss was 22.24 %. Anti-A/B antibody titre and plasma content were significantly lower in CPP. CPP were characterised by faster clot initiation and form stable PLT clots. The number of PLT microparticles increased 25 times in CPP and there were more particles positive for the activation marker CD62 P compared to FP. CONCLUSION: Thawing and reconstitution are easy and fast processes if platelet additive solution is used. Low anti-A/B antibody titre and plasma content make possible the use of CPP of blood group O reconstituted in SSP + as universal ABO products, including clinical situations where washed PLTs are required. Clot properties evaluated via rotational thromboelastometry demonstrated that CPP retain a significant part of their activity compare to FP and are haemostatically effective.
- MeSH
- hemostáza MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- trombocyty metabolismus MeSH
- vrstva buffy coat metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Mental imagery related to the recent death of a loved one is associated with intense sadness and distress. Social relations, such as with one's significant other, can regulate negative emotions and provide comfort, but the neural correlates of social comfort are largely unknown. In this functional magnetic resonance imaging study, we examined brain responses to sad mental imagery and how these are modulated by holding hands with one's romantic partner. We found that mental imagery of a recently deceased loved one was associated with increased reactivity in the dorsal striatum, medial prefrontal cortex, anterior and posterior cingulate cortex, thalamus and cerebellum. Holding hands with one's partner as compared to being alone or holding hands with a stranger provided subjective comfort and reduced neural reactivity in the dorsal striatum without affecting the vividness of the imagery. Our findings indicate an important role for the dorsal striatum in sad mental imagery and social comfort and suggest that tactile social support by one's romantic partner regulates subjective distress through other processes than mere distraction from the mental imagery.
- MeSH
- cingulární gyrus diagnostické zobrazování fyziologie MeSH
- dospělí MeSH
- hmatová percepce fyziologie MeSH
- imaginace fyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- mozeček diagnostické zobrazování fyziologie MeSH
- neostriatum diagnostické zobrazování fyziologie MeSH
- prefrontální mozková kůra diagnostické zobrazování fyziologie MeSH
- připoutání k objektu * MeSH
- sexuální partneři MeSH
- smutek fyziologie MeSH
- sociální opora * MeSH
- thalamus diagnostické zobrazování fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BRAF inhibitors can delay the progression of metastatic melanoma, but resistance usually emerges, leading to relapse. Drugs simultaneously targeting two or more pathways essential for cancer growth could slow or prevent the development of resistant clones. Here, we identified pyridinyl imidazole compounds SB202190, SB203580, and SB590885 as dual inhibitors of critical proliferative pathways in human melanoma cells bearing the V600E activating mutation of BRAF kinase. We found that the drugs simultaneously disrupt the BRAF V600E-driven extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) activity and the mechanistic target of rapamycin complex 1 (mTORC1) signaling in melanoma cells. Pyridinyl imidazole compounds directly inhibit BRAF V600E kinase. Moreover, they interfere with the endolysosomal compartment, promoting the accumulation of large acidic vacuole-like vesicles and dynamic changes in mTOR signaling. A transient increase in mTORC1 activity is followed by the enrichment of the Ragulator complex protein p18/LAMTOR1 at contact sites of large vesicles and delocalization of mTOR from the lysosomes. The induced disruption of the endolysosomal pathway not only disrupts mTORC1 signaling, but also renders melanoma cells sensitive to endoplasmic reticulum (ER) stress. Our findings identify new activities of pharmacologically relevant small molecule compounds and provide a biological rationale for the development of anti-melanoma therapeutics based on the pyridinyl imidazole core.
- Publikační typ
- časopisecké články MeSH
Different approaches to enhance healing of hard or soft tissues include the use of cytokines and growth factors to modify cellular behaviour. Numerous growth factors are found in autologous blood concentrates - platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). Enamel matrix derivative (EMD) may improve tissue healing via amelogenins. Bilayered collagen matrix (CM) is used for soft tissue augmentation. The aim of the present study was to assess potential benefits of PRP, PRF and EMD in combination with bilayered collagen matrix or CM alone in treatment of oral mucosal defects in rabbits. Twenty-seven New Zealand white rabbits were included in this randomized controlled trial. Artificial oral mucosal defects were treated with one of these five approaches: PRP+CM, PRF+CM, EMD+CM, CM alone, or left untreated as a negative control - CO. The animals were euthanized 1 day, 7 days, or 28 days after surgery and necropsies were harvested. Histological and molecular biological analyses were performed. All defects were healed by day 28. No differences between PRP+CM, PRF+CM, CM alone and CO groups were recorded at any time point. Slower angiogenesis and a higher presence of inflammatory infiltrate were observed in the EMD+CM group 28 days after surgery. Molecular biological analyses did not reveal any statistically significant changes. In conclusion, no improvement in mucosal healing of wounds covered with a collagen membrane and PRP, PRF, or EMD was observed, compared with CM alone or untreated controls.
INTRODUCTION: Hypokinetic dysarthria (HD) is a common symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated acute effects of repetitive transcranial magnetic stimulation (rTMS) of the motor and auditory feedback area on HD in PD using acoustic analysis of speech. METHODS: We used 10 Hz and 1 Hz stimulation protocols and applied rTMS over the left orofacial primary motor area, the right superior temporal gyrus (STG), and over the vertex (a control stimulation site) in 16 PD patients with HD. A cross-over design was used. Stimulation sites and protocols were randomised across subjects and sessions. Acoustic analysis of a sentence reading task performed inside the MR scanner was used to evaluate rTMS-induced effects on motor speech. Acute fMRI changes due to rTMS were also analysed. RESULTS: The 1 Hz STG stimulation produced significant increases of the relative standard deviation of the 2nd formant (p = 0.019), i.e. an acoustic parameter describing the tongue and jaw movements. The effects were superior to the control site stimulation and were accompanied by increased resting state functional connectivity between the stimulated region and the right parahippocampal gyrus. The rTMS-induced acoustic changes were correlated with the reading task-related BOLD signal increases of the stimulated area (R = 0.654, p = 0.029). CONCLUSION: Our results demonstrate for the first time that low-frequency stimulation of the temporal auditory feedback area may improve articulation in PD and enhance functional connectivity between the STG and the cortical region involved in an overt speech control.
- MeSH
- akustika řeči MeSH
- dysartrie diagnostické zobrazování etiologie patofyziologie MeSH
- gyrus parahippocampalis diagnostické zobrazování patofyziologie MeSH
- konektom * MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- motorické korové centrum diagnostické zobrazování patofyziologie MeSH
- nervová síť diagnostické zobrazování patofyziologie MeSH
- Parkinsonova nemoc komplikace diagnostické zobrazování patofyziologie MeSH
- senioři MeSH
- senzorická zpětná vazba fyziologie MeSH
- spánkový lalok diagnostické zobrazování patofyziologie MeSH
- transkraniální magnetická stimulace * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
