OBJECTIVES: Minimal residual disease (MRD) status in multiple myeloma (MM) is an important prognostic biomarker. Personalized blood-based targeted mass spectrometry detecting M-proteins (MS-MRD) was shown to provide a sensitive and minimally invasive alternative to MRD-assessment in bone marrow. However, MS-MRD still comprises of manual steps that hamper upscaling of MS-MRD testing. Here, we introduce a proof-of-concept for a novel workflow using data independent acquisition-parallel accumulation and serial fragmentation (dia-PASEF) and automated data processing. METHODS: Using automated data processing of dia-PASEF measurements, we developed a workflow that identified unique targets from MM patient sera and personalized protein sequence databases. We generated patient-specific libraries linked to dia-PASEF methods and subsequently quantitated and reported M-protein concentrations in MM patient follow-up samples. Assay performance of parallel reaction monitoring (prm)-PASEF and dia-PASEF workflows were compared and we tested mixing patient intake sera for multiplexed target selection. RESULTS: No significant differences were observed in lowest detectable concentration, linearity, and slope coefficient when comparing prm-PASEF and dia-PASEF measurements of serial dilutions of patient sera. To improve assay development times, we tested multiplexing patient intake sera for target selection which resulted in the selection of identical clonotypic peptides for both simplex and multiplex dia-PASEF. Furthermore, assay development times improved up to 25× when measuring multiplexed samples for peptide selection compared to simplex. CONCLUSIONS: Dia-PASEF technology combined with automated data processing and multiplexed target selection facilitated the development of a faster MS-MRD workflow which benefits upscaling and is an important step towards the clinical implementation of MS-MRD.
- MeSH
- automatizace MeSH
- individualizovaná medicína metody MeSH
- lidé MeSH
- mnohočetný myelom * diagnóza krev MeSH
- průběh práce * MeSH
- reziduální nádor * diagnóza MeSH
- rychlé screeningové testy metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
... Odnos sestara prema informatizaciji: javno zdravstveni značaj. (10 min.) -- 11. ...
1 CD-ROM (1 textový soubor) ; 12 cm
Płyta CD to zbiór prac przedstawionych na kongresie poświęconym rehabilitacji i fizjoterapii COVID-19. Przeznaczona dla profesjonalnej publiczności. CD je zborníkom prác prednesených na kongrese, ktorý sa zameral na rehabilitáciu a fyzioterapiu COVID-19. Určené odbornej verejnosti.
- MeSH
- COVID-19 rehabilitace MeSH
- rehabilitace MeSH
- techniky fyzikální terapie MeSH
- Publikační typ
- kongresy MeSH
- sborníky MeSH
- zprávy MeSH
- Konspekt
- Fyzioterapie. Psychoterapie. Alternativní lékařství
- NLK Obory
- rehabilitační a fyzikální medicína
- pneumologie a ftizeologie
- NLK Publikační typ
- CD-ROM
INTRODUCTION AND HYPOTHESIS: The main risk factor for pelvic floor disorders is vaginal delivery, which may cause levator ani muscle (LAM) injury and denervation. LAM includes pubovisceral muscle (PVM, pubococcygeus), puborectalis muscle (PRM), and iliococcygeus muscle. We hypothesize that primiparous women with low pelvic floor muscle contraction have a reduced PVM cross-sectional area (CSA) compared to nulliparous women. METHODS (SAMPLE SIZE AND STATISTICAL APPROACHES): This single-centre prospective observational study compared healthy nulliparous (n = 40) to primiparous (n = 40) women after vaginal delivery without LAM avulsion and Oxford score ≤ 3. Demographics, questionnaires (ICIQ-UI-SF, OAB-Q-SF, PISQ-12), POP-Q, Oxford score, ultrasound measurements (minimal anteroposterior and lateral diameters, hiatal area, PRM thickness, levator-urethra gap) and magnetic resonance imaging (MRI)-PVM CSA were evaluated. Normality was tested, and an appropriate test was used to compare the groups. Power calculation suggested 40 participants per group. RESULTS: The primiparous group was older, had a higher BMI, and their hiatal area on ultrasound at contraction was larger compared to the nulliparous group. The CSA of the left-sided PVM (1.15 ± 0.50 cm2) was larger compared to the right side (1.03 ± 0.50 cm2), p = 0.02 in nulliparous women. The PVM CSA of primiparous women with low Oxford score was reduced compared to nulliparous (0.87 ± 0.30 versus 1.09 ± 0.50 cm2, p = 0.006). The intra-rater reliability for PVM CSA had an ICC of 0.90 and inter-rater ICC of 0.77. CONCLUSIONS: Primiparous women after vaginal delivery with low pelvic floor contraction force had reduced PVM CSA on MRI images compared to nulliparous women.
- MeSH
- dospělí MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- onemocnění dna pánevního diagnostické zobrazování etiologie MeSH
- pánevní dno * diagnostické zobrazování MeSH
- parita * MeSH
- prospektivní studie MeSH
- svalová kontrakce fyziologie MeSH
- těhotenství MeSH
- ultrasonografie MeSH
- vedení porodu MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Tick-borne encephalitis virus (TBEV) is a major cause of neurological infections in many regions of central, eastern and northern Europe and northern Asia. In approximately 15% of cases, TBEV infections lead to the development of severe encephalitis or meningitis. The main route of TBEV transmission is tick bites; however, ingestion of dairy products from infected animals (goats, cattle and sheep) is also a frequent cause of the disease. Therefore, vaccination of livestock in virus endemic regions could also contribute to the decrease in TBEV infection among humans. Although few vaccines against TBEV based on inactivated viruses are available for humans, due to high costs, vaccination is not mandatory in most of the affected countries. Moreover, there is still no vaccine for veterinary use. Here, we present a characterization and immunogenicity study of a new potential TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells. VLPs, which mimic native viral particles but do not contain genetic material, show good immunogenic potential. For the first time, we showed that the protozoan L. tarentolae expression system can be successfully used for the production of TBEV virus-like particles with highly efficient production. We confirmed that TBEV recombinant structural proteins (prM/M and E) from VLPs are highly recognized by neutralizing antibodies in in vitro analyses. Therefore, VLPs in combination with AddaVax adjuvant were used in immunization studies in a mouse model. VLPs proved to be highly immunogenic and induced the production of high levels of neutralizing antibodies. In a challenge experiment, immunization with VLPs provided full protection from lethal TBE in mice. Thus, we suggest that Leishmania-derived VLPs may be a good candidate for a safe alternative human vaccine with high efficiency of production. Moreover, this potential vaccine candidate may constitute a low-cost candidate for veterinary use.
- MeSH
- klíšťová encefalitida * prevence a kontrola MeSH
- Leishmania * MeSH
- lidé MeSH
- myši MeSH
- neutralizující protilátky MeSH
- ovce MeSH
- protilátky virové MeSH
- skot MeSH
- virové vakcíny * MeSH
- viry klíšťové encefalitidy * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION AND HYPOTHESIS: Injury of the levator ani muscle (LAM) is a significant risk factor for pelvic organ prolapse (POP). The puborectalis (PRM) and pubovisceral (PVM) subdivisions are level III vaginal support structures. The null hypothesis was that there is no significant difference in patterns of LAM subdivisions in healthy nulliparous women. Secondarily, we evaluated the presence of different LAM injury in a POP-symptomatic cohort. METHODS: This retrospective magnetic resonance imaging study included: 64 nulligravidae without any pelvic floor dysfunction (PFD) and 526 women of various parity with symptomatic POP. Primary outcome was PVM and PRM morphology on the axial planes: the attachment site on the pubic bone, and the visible separation/border between the PVM and PRM. The attachment was scored as "normal" or "abnormal". The "abnormal" attachment was divided in two types: "type I"-loss of the muscle substance, but preservation of the overall muscle architecture-and "type II"-muscle detachment from the pubic bone. RESULTS: The puboanal muscle (PAM) subdivision was evaluated as a representative part of the PVM. The PAM and PRM attachments and separation were distinguished in all asymptomatic nulliparae. PAM and PRM attachments did not significantly differ. POP group characteristics were parity 1.9 ± 0.8, instrumental delivery 5.6%, hysterectomy or POP surgery 60%, all Pelvic Organ Prolapse Quantification (POP-Q) stages, LAM defect 77.6% (PRM: 77.1%; PAM: 51.3%). Type I injuries were more frequent (PRM 54.7%; PAM 53.9%) compared with type II (PRM 29.4%; PAM 42.1%). CONCLUSIONS: A LAM defect was present in 77.6% of women with symptomatic POP. In PRM and PAM subdivisions type I injury was more frequent than type II.
- MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- pánevní dno zranění MeSH
- prolaps pánevních orgánů * diagnostické zobrazování etiologie MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- vagina * diagnostické zobrazování MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151-202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks. METHODS: Patients who completed the randomized PRM-151-202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis). RESULTS: All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, - 6.2% (- 7.7; - 4.6) and - 5.7% (- 8.0; - 3.3) for percent predicted FVC and - 36.3 m (- 65.8; - 6.9) and - 28.9 m (- 54.3; - 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128. CONCLUSIONS: Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.
Parallel reaction monitoring (PRM) has emerged as a popular approach for targeted protein quantification. With high ion utilization efficiency and first-in-class acquisition speed, the timsTOF Pro provides a powerful platform for PRM analysis. However, sporadic chromatographic drift in peptide retention time represents a fundamental limitation for the reproducible multiplexing of targets across PRM acquisitions. Here, we present PRM-LIVE, an extensible, Python-based acquisition engine for the timsTOF Pro, which dynamically adjusts detection windows for reproducible target scheduling. In this initial implementation, we used iRT peptides as retention time standards and demonstrated reproducible detection and quantification of 1857 tryptic peptides from the cell lysate in a 60 min PRM-LIVE acquisition. As an application in functional proteomics, we use PRM-LIVE in an activity-based protein profiling platform to assess binding selectivity of small-molecule inhibitors against 220 endogenous human kinases.
Cerebral palsy (CP) is a group of the most common developmental disorders affecting movement and posture of the body, causing activity limitations and participation restrictions. The motor disorders of persons with CP are often accompanied by disturbances of sensation, cognition, communication and perception. The symptoms of CP are very diverse and persons with CP are usually presented with a mixed type of symptoms. The non-progressive disturbances can be attributed to disorders that were developed during pregnancy, birth and/or infant stage. The aim of this study was to improve physicians' professional practice of Physical and Rehabilitation Medicine for persons with cerebral palsy in order to improve their functionality, social and community integration, and to reduce activity limitations and/or participation restrictions. A systematic review of the literature including an 18-year period and consensus procedure by means of a Delphi process was performed and involved the delegates of all European countries represented in the Union of European Medical Specialists Physical and Rehabilitation Medicine (UEMS PRM) Section. As the result of a Consensus Delphi procedure, 74 recommendations are presented together with the systematic literature review. The PRM physician's role for persons with cerebral palsy is to lead and coordinate the multiprofessional team, working in an interdisciplinary way. They should propose and manage the complex but individual PRM program developed in conjunction with other health professionals, medical specialists and importantly in agreement with the patient, their family and care giver. This should be, according to the specific medical diagnosis to improve patients' health, functioning, social and education status, considering all impairments, comorbidities and complications, activity limitations and participation restrictions. This evidence-based position paper is representing the official position of The European Union through the UEMS PRM Section and designates the professional role of PRM physicians in persons with cerebral palsy.
- MeSH
- lidé MeSH
- mozková obrna * MeSH
- odborná praxe MeSH
- rehabilitační lékařství * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- Geografické názvy
- Evropa MeSH
Míč letící od soupeře má pokaždé jinou rychlost a trajektorii, ale i na nižší kategorii turnajů hráč musí rychle reagovat, aby ho zvládl správně odehrát. Cílem je porovnat, jak se liší tempo hry a vybrané herní charakteristiky na antukovém a tvrdém povrchu na mezinárodních turnajích nižší kategorie. Porovnáváme mezi sebou dva mezinárodní turnaje tenisu mužů stejné kategorie ITF Men's World Tennis Tour. Na turnaji Milovice Open 2019 (tvrdý povrch) jsme analyzovali 1629 rozeher v 15 náhodně vybraných utkáních. Druhým turnajem byl RPM Prague Open 2019 hraný na antuce. V deseti analyzovaných utkáních se odehrálo 1296 rozeher. Výsledky ukázaly, že průměrné tempo hry bylo významně rychlejší na Milovice Open (1,27 ± 0,05 s) oproti RPM Open (1,32 ± 0,05 s) t(23) = 2,68, p < 0,05, (d = 1,20); a dosáhlo se významně rozdílného poměru zatížení a pauzy na Milovice Open (1:3,72 ± 0,75) ve srovnání s RPM Open (1:3,02 ± 0,60) t(23) = -2,25, p < 0,05, (d = 0,94). Na Milovice Open byla rozehra ukončena častěji do čtvrtého úderu (61 %) než na PRM Open (53 %). Tato studie ukazuje na vybrané herní charakteristiky hry na nižších kategoriích mezinárodních turnajů mužů a porovnává je na tvrdém a antukovém povrchu. Zjištěné informace mohou být užitečné z trenérského i hráčského pohledu.
Even on a lower level of tennis tournament, a player has a very short time to hit an incoming ball as the ball travels quickly and has various ball trajectory. The aim is to compare the rally pace and selected match characteristics between the clay and hard court at the lower level of international tennis tournaments. We compare two ITF Men's World Tennis Tour tournaments - the Milovice Open (hard court) and the RPM Open (clay court). We analysed 1629 points in 15 matches at the Milovice Open and 1296 points in 10 matches at RPM Open. The results showed that the rally pace was significantly faster at the Milovice Open (1,27 ± 0,05 s) compared RPM Open (1,32 ± 0,05 s) t(23) = 2,68, p < 0,05, (d = 1,20); and also significant difference was found in the work/rest ratio between the Milovice Open (1:3,72 ± 0,75) and the RPM Open (1:3,02 ± 0,60) t(23) = -2,25, p < 0,05, (d = 0,94). The rally was finished within the first 4 shots in 61% at the Milovice Open compared to 53% at the RPM Open. This study shows and compares selected match characteristics on lower level of international tennis tournaments in men's tennis. We found some interesting information, that can be useful for players and coaches.
- Klíčová slova
- tennis, notational analyses, game performance, load, strategy, tenis, notační analýza, herní výkon, zatížení, strategie,
- MeSH
- lidé MeSH
- tenis MeSH
- Check Tag
- lidé MeSH
The growing consumption of pharmaceuticals in the human population and the insufficient efficiency of their elimination in waste water has a long-term negative impact on the environment of aquatic ecosystems, including the organisms that inhabit them. A significant contributor is the consumption of anti-depressants from the SSRI group, which corresponds to their increasing concentration in the environment. The aim of this work was to determine if antidepressant sertraline is able to be stored in fish organisms and to evaluate the content of residues in various body tissues. Rainbow trout (Oncorhynchuss mykkis) was selected as the test organism and was artificially exposed to the antidepressant for 1 month (concentrations 0; 4.2; 44 and 400 ng.g-1 sertraline in the feed). Liver, kidney, brain and muscle tissue biopsies samples were taken for analysis. Detection was performed using an Accela 1250 LC pump and an Accela autosampler coupled with a high-performance mass analyzer with a heated electrospray ionization source Q-Exactive Orbitrap, operating in positive ionization mode and in PRM mode (m/z 306.08108->275.03888 and 309.009991->275.03888 for sertraline and internal standard, respectively). The limit of quantification of the method was 0.1 ng.g-1 of sertraline and the calibration curve showed a good linearity up to 20 ng.g-1. From the collected data, amount of residues was found in the liver, kidney and brain. In contrast, the incidence of residues in muscle tissue was not detected in all groups, which is favorable from the point of view of fish meat consumption, by humans.
- MeSH
- chemické látky znečišťující vodu analýza MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací * MeSH
- obsah radioaktivních látek v organizmu MeSH
- Oncorhynchus mykiss metabolismus MeSH
- rezidua léčiv analýza MeSH
- selektivní inhibitory zpětného vychytávání serotoninu analýza MeSH
- sertralin analýza MeSH
- tandemová hmotnostní spektrometrie * MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
