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Súhrn: Určiť diagnostický význam parametrov pulzatility index (PI) a rezistens index (RI) vo fetálnejaorte počas tehotnosti s detekovanou intrauterinnou retardáciou rastu (IUGR). Vyšetrenia- ABUSONIC 8, ALOKA 680 SSD, transabdominálnou 3,5 MHz sondou s farebným dopplerovskýmmodulom.Názov a sídlo pracoviska: II. Gynekologicko-pôrodnícka klinika, LF UPJŠ a FN L. Pasteura, Košice,Slovenská republika, Obst/Gynae Dpt., Victoria Hospital, Mahé, Seychelles Republic, IndianaOcean.Súbor a metóda: Vyhodnotili sme prospektívnu komparatívnu štúdiu dvoch skupín rizikových tehotností.Skupina A 112 gravidít s klinickými známkami preeklampsie s detekovanou IUGR plodu, ktorúsme podľa klasifi kácie foriem preeklampsie na miernu, strednú a ťažkú diferencovali na podskupinyA1 A2, A3 a A4 s eklampsiou a komparatívnu skupinu B 106 gravidít. V skupinách sme vyhodnocovaliPI, RI aorta descendens v oblasti bifurkácie v priebehu gestácie od 28. týždňa až do ukončenia gravidity.Parametre boli merané v týždňových intervaloch podľa klinického ultrasonografi ckého protokolu.Porovnali sme priemerne hodnoty PI, RI v priebehu gravidity v skupine A a skupine B v korešpondujúcichtýždňoch gravidity. V podskupinách-A1, A2, A3 sme vyhodnotili výskyt plodov s IUGR.Výsledky: Aorta descendens PI, RI vykazuje u plodov v skupine A signifi kantne vyššie priemernehodnoty PI, RI oproti komparatívnej skupine B. V skupine A sme nezaznamenali zníženie rezistenciev descendentnej aorte po 34. týždni tehotenstva. V komparatívnej skupine B po 34. týždnisignifi kantne hodnoty PI, RI klesajú. Z celkového počtu 112 tehotenstiev v skupine A s preeklampsioua eklampsiou vykazovalo až 52,6 % retardáciu prírastku bioparametrov - IUGR, aleboreštrikciu a nulový prírastok. V podskupine A1 ľahkých foriem preeklampsie to bolo 20,5 %detekovaných plodov s IUGR. V podskupine A2 stredných foriem preeklampsie to bolo 51,3 % plodov a v podskupine A3 ťažkých foriem až 87,8 % plodov s IUGR alebo reštrikciou prírastku.U všetkých 3 plodov pri eklampsii. Podskupina A4 išlo o reštrikciu rastu a reverzný tok v descendentnejaorte.Hlavný záver: Funkčné vyšetrenie prietoku v descendentnej fetálnej aorte je súčasťou komplexnejanalýzy fetálnej cirkulácie v rámci nadstavbového ultrazvukového protokolu a je významnoumetódou na diferenciáciu rizikových gravidít so suspektným ohrozením plodu a intrauterinnourastovou retardáciou. Relatívne nízky podiel IUGR v skupine dáva možnosť dobrej prognózy rastupri efektívnej vazodilatačnej liečbe.
Summary pregnancycomplicated by ultrasonografi cally detected intrauterine growth retardation-IUGR.Setting: Dpt. of Obstetric and Gynaecology, Safarik‘s University and University Hospital L. Pasteur,Kosice, Slovak Republic, Obst/Gynae Dpt., Victoria Hospital, Mahé, Seychelles Republic,Indian Ocean.Subject and Method: The autors measured fetal circulation on the level of descending aortal bifurcation.The results were compared in the Group-A of 112 pregnancies complicated by mild,moderate and several praeeclampsia, eclampsia with detected IUGR, and comparative Group-Bof 106 pregnancies.Intervention: The ACUSONIC 8, ALOKA 680 SSD using transabdominal 3.5 MHz probe with collordoppler facility. The parameters were measured in weekly intervals according the clinical protocolfor management of high risk pregnancies.Subjects: There was opened a prospective comparative study of 112 risk pregnancies (Group-A) anda comparative Group-B of 106 pregnancies with normal growth of fetuses. Group-A was devided accordingclassifi cation of praeeclampsia to Subgroup-A1, mild praeeclampsia, Subgroup-A2, moderatepraeeclampsia, Subgroup-A3, severe praeclampsia and Subgroup-A4, eclampsia. Parameters of vascularresistance in descending aorta were calculated from 28th week of gestation to termination ofpregnancy and compared average values in corresponding stage in the Group-A and the comparativeGroup-B. Number of IUGR fetuses or restricted with the growth were calculated in Subgroups - A.Results: Descending aorta presents signifi cantly higher average values of PI, RI during pregnancyfrom 28th week of gestation in Group-A. There is no evidence of diastolic decrease after 34thweek of gestation in Group-A. In Group-A 52.6% fetuses were ultrasonografi caly IUGR detected orrestricted. In Subgroup-A1 of mild praeeclampsia were 20.5% of the IUGR fetuses. Subgroup-A2 ofmoderate praeeclampsia showed 51.3% and Subgroup-A3 severe praeeclampsia 87.8% of the IUGRfetuses of restricted. Three cases of eclampsia were restricted for growth .Main outcome - functional assessment of the descending aorta fl ow is the most reliable method fordifferentiation of praeclamptic and eclamptic pregnancies with suspected fetal starvation andintrauterine growth retardation.
- MeSH
- aorta MeSH
- dospělí MeSH
- komplikace těhotenství diagnóza patologie MeSH
- lidé MeSH
- preeklampsie patologie MeSH
- pulzatilní průtok MeSH
- růstová retardace plodu diagnóza patologie MeSH
- srdeční frekvence plodu MeSH
- těhotenství MeSH
- ultrasonografie dopplerovská barevná metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
beta-catenin has a dual function; it is implicated in intercellular junctions and transcriptional co-activation. Here we examined the regulation of the expression and localization of beta-catenin in HT29 colorectal adenocarcinoma cells. Our results showed that inhibition of PI-3 kinase with wortmannin was accompanied by a considerably reduced expression of beta-catenin. This effect was overcome by butyrate and occurred at the protein level, not at the level of mRNA. Moreover, NaBT significantly increased the phosphorylation of the ribosomal protein, S6, known to participate in the translational control of gene expression. This was accompanied by the increased phosphorylation of p70 S6K and MAPKs, the effector proteins that are upstream of protein S6 in the distinct signaling pathways. These facts indicate that different signaling pathways may be involved in the regulation of beta-catenin synthesis. Modulation of beta-catenin expression induced by NaBT appeared to occur at the level of protein translation, suggesting that NaBT may act as a translational regulator.
- MeSH
- adenokarcinom metabolismus MeSH
- alkalická fosfatasa metabolismus MeSH
- androstadieny metabolismus MeSH
- beta-katenin genetika metabolismus MeSH
- butyráty metabolismus MeSH
- financování organizované MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- fosforylace MeSH
- imunohistochemie MeSH
- inhibitory fosfoinositid-3-kinasy MeSH
- kinasy ribozomálního proteinu S6, 70-kDa metabolismus MeSH
- kinasy ribozomálního proteinu S6 metabolismus MeSH
- kolorektální nádory metabolismus MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- nádorové buněčné linie MeSH
- serin metabolismus MeSH
- signální transdukce fyziologie MeSH
- tyrosin metabolismus MeSH
- Check Tag
- lidé MeSH
[Figure: see text].
- MeSH
- biologická evoluce MeSH
- buněčné linie MeSH
- cytokineze * MeSH
- dánio pruhované MeSH
- endozomální třídící komplexy pro transport metabolismus MeSH
- fosfatidylinositol-3-kinasy genetika metabolismus MeSH
- fosfatidylinositol-4,5-difosfát metabolismus MeSH
- fosfatidylinositoly metabolismus MeSH
- katarakta metabolismus patologie MeSH
- lidé MeSH
- mutace MeSH
- myši MeSH
- oční čočka cytologie růst a vývoj metabolismus MeSH
- předčasné stárnutí MeSH
- proteiny buněčného cyklu metabolismus MeSH
- proteiny dánia pruhovaného genetika metabolismus MeSH
- proteiny vázající vápník metabolismus MeSH
- stárnutí buněk * MeSH
- tubulin metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a lamin A/C pool with specific properties and distinct functions. Nucleoplasmic lamin A/C molecular functions are mainly dependent on its binding partners; therefore, revealing new interactions could give us new clues on the lamin A/C mechanism of action. In the present study, we show that lamin A/C interacts with nuclear phosphoinositides (PIPs), and with nuclear myosin I (NM1). Both NM1 and nuclear PIPs have been previously reported as important regulators of gene expression and DNA damage/repair. Furthermore, phosphorylated lamin A/C forms a complex with NM1 in a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent manner in the nuclear interior. Taken together, our study reveals a previously unidentified interaction between phosphorylated lamin A/C, NM1, and PI(4,5)P2 and suggests new possible ways of nucleoplasmic lamin A/C regulation, function, and importance for the formation of functional nuclear microdomains.
- MeSH
- buněčné jádro * metabolismus MeSH
- interfáze MeSH
- intermediární filamenta metabolismus MeSH
- lamin typ A * metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
STUDY QUESTION: Is it possible to define a set of performance indicators (PIs) for clinical work in ART, which can create competency profiles for clinicians and for specific clinical process steps? SUMMARY ANSWER: The current paper recommends six PIs to be used for monitoring clinical work in ovarian stimulation for ART, embryo transfer, and pregnancy achievement: cycle cancellation rate (before oocyte pick-up (OPU)) (%CCR), rate of cycles with moderate/severe ovarian hyperstimulation syndrome (OHSS) (%mosOHSS), the proportion of mature (MII) oocytes at ICSI (%MII), complication rate after OPU (%CoOPU), clinical pregnancy rate (%CPR), and multiple pregnancy rate (%MPR). WHAT IS KNOWN ALREADY: PIs are objective measures for evaluating critical healthcare domains. In 2017, ART laboratory key PIs (KPIs) were defined. STUDY DESIGN SIZE DURATION: A list of possible indicators was defined by a working group. The value and limitations of each indicator were confirmed through assessing published data and acceptability was evaluated through an online survey among members of ESHRE, mostly clinicians, of the special interest group Reproductive Endocrinology. PARTICIPANTS/MATERIALS SETTING METHODS: The online survey was open for 5 weeks and 222 replies were received. Statements (indicators, indicator definitions, or general statements) were considered accepted when ≥70% of the responders agreed (agreed or strongly agreed). There was only one round to seek levels of agreement between the stakeholders.Indicators that were accepted by the survey responders were included in the final list of indicators. Statements reaching less than 70% were not included in the final list but were discussed in the paper. MAIN RESULTS AND THE ROLE OF CHANCE: Cycle cancellation rate (before OPU) and the rate of cycles with moderate/severe OHSS, calculated on the number of started cycles, were defined as relevant PIs for monitoring ovarian stimulation. For monitoring ovarian response, trigger and OPU, the proportion of MII oocytes at ICSI and complication rate after OPU were listed as PIs: the latter PI was defined as the number of complications (any) that require an (additional) medical intervention or hospital admission (apart from OHSS) over the number of OPUs performed. Finally, clinical pregnancy rate and multiple pregnancy rate were considered relevant PIs for embryo transfer and pregnancy. The defined PIs should be calculated every 6 months or per 100 cycles, whichever comes first. Clinical pregnancy rate and multiple pregnancy rate should be monitored more frequently (every 3 months or per 50 cycles). Live birth rate (LBR) is a generally accepted and an important parameter for measuring ART success. However, LBR is affected by many factors, even apart from ART, and it cannot be adequately used to monitor clinical practice. In addition to monitoring performance in general, PIs are essential for managing the performance of staff over time, and more specifically the gap between expected performance and actual performance measured. Individual clinics should determine which indicators are key to the success in their organisation based on their patient population, protocols, and procedures, and as such, which are their KPIs. LIMITATIONS REASONS FOR CAUTION: The consensus values are based on data found in the literature and suggestions of experts. When calculated and compared to the competence/benchmark limits, prudent interpretation is necessary taking into account the specific clinical practice of each individual centre. WIDER IMPLICATIONS OF THE FINDINGS: The defined PIs complement the earlier defined indicators for the ART laboratory. Together, both sets of indicators aim to enhance the overall quality of the ART practice and are an essential part of the total quality management. PIs are important for education and can be applied during clinical subspecialty. STUDY FUNDING/COMPETING INTERESTS: This paper was developed and funded by ESHRE, covering expenses associated with meetings, literature searches, and dissemination. The writing group members did not receive payment.Dr G.G. reports personal fees from Merck, MSD, Ferring, Theramex, Finox, Gedeon-Richter, Abbott, Biosilu, ReprodWissen, Obseva, PregLem, and Guerbet, outside the submitted work. Dr A.D. reports personal fees from Cook, outside the submitted work; Dr S.A. reports starting a new employment in May 2020 at Vitrolife. Previously, she has been part of the Nordic Embryology Academic Team, with meetings were sponsored by Gedeon Richter. The other authors have no conflicts of interest to declare. DISCLAIMER: This document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation.The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type.Furthermore, ESHREs recommendations do not constitute or imply the endorsement, recommendation, or favouring of any of the included technologies by ESHRE.
- Publikační typ
- časopisecké články MeSH
Childhood T-cell acute lymphoblastic leukemia (T-ALL) still remains a therapeutic challenge due to relapses which are resistant to further treatment. L-asparaginase (ASNase) is a key therapy component in pediatric T-ALL and lower sensitivity of leukemia cells to this drug negatively influences overall treatment efficacy and outcome. PTEN protein deletion and/or activation of the PI3K/Akt signaling pathway leading to altered cell growth and metabolism are emerging as a common feature in T-ALL. We herein investigated the relationship amongst PTEN deletion, ASNase sensitivity and glucose metabolism in T-ALL cells. First, we found significant differences in the sensitivity to ASNase amongst T-ALL cell lines. While cell lines more sensitive to ASNase were PTEN wild type (WT) and had no detectable level of phosphorylated Akt (P-Akt), cell lines less sensitive to ASNase were PTEN-null with high P-Akt levels. Pharmacological inhibition of Akt in the PTEN-null cells rendered them more sensitive to ASNase and lowered their glycolytic function which then resembled PTEN WT cells. In primary T-ALL cells, although P-Akt level was not dependent exclusively on PTEN expression, their sensitivity to ASNase could also be increased by pharmacological inhibition of Akt. In summary, we highlight a promising therapeutic option for T-ALL patients with aberrant PTEN/PI3K/Akt signaling.
- MeSH
- asparaginasa * farmakologie terapeutické užití MeSH
- dítě MeSH
- fosfatidylinositol-3-kinasy * genetika metabolismus MeSH
- fosfohydroláza PTEN * genetika metabolismus MeSH
- lidé MeSH
- lymfoblastická leukemie-lymfom z prekurzorových T-buněk * farmakoterapie genetika metabolismus MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- signální transdukce MeSH
- T-lymfocyty metabolismus MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The diagnostic accuracy of prostate magnetic resonance imaging (MRI) is highly dependent on image quality. Although the effects of spasmolytics and rectal preparation have been previously studied, the findings remain inconsistent and fail to address other critical modifiable factors. This study aimed to evaluate the impact of various modifiable factors on prostate MRI image quality and their subsequent influence on Prostate Imaging Reporting and Data System (PI-RADS) scoring. METHODS: Fifty-six consecutive patients who underwent 3T multiparametric MRI (mpMRI) with the administration of hyoscine butylbromide (HB+) and at least one 3T mpMRI without HB (HB-) ≤3 years earlier were retrospectively evaluated. Two radiologists performed morphometry of the prostate, bladder, rectum, and abdomen and evaluated image quality, artifacts, and motion on a five-point scale and T2 and diffusion-weighted imaging (DWI) PI-RADS v2.1 scores. The influence of HB, rectum and bladder distension, breathing motion, and examination hour were analyzed. RESULTS: The sharpness and overall image quality of T2 images were significantly better in HB+ compared to HB- (P=0.0047 and P=0.013). T2 motion artifacts were reduced earlier in the day (ρ=0.32, P=0.017). DWI susceptibility artifact correlated with patient diameter (ρ=0.40, P=0.002), but not with rectum diameter (ρ=0.09, P=0.51) or gas content (ρ=0.13, P=0.33). Examinations later in the day were associated with increased motion artifacts on T2 [hazard ratio (HR) =1.36]. T2 and DWI scores were influenced by bladder volume, breathing motion, and rectal air, but not by HB. Breathing motion negatively impacted overall image quality (HR =1.24), and DWI susceptibility artifacts (HR =1.22). CONCLUSIONS: HB administration, daytime, and breathing motion have significant influence on image quality of prostate MRI. The gas content of the rectum influences T2 image quality and T2 scores. Bladder filling is associated with reduced breathing motion, subsequently affecting DWI scores.
- Publikační typ
- časopisecké články MeSH
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a critically important regulatory lipid of the plasma membrane (PM); however, little is known about how cells regulate PM PI(4,5)P2 levels. Here, we show that the phosphatidylinositol 4-phosphate (PI4P)/phosphatidylserine (PS) transfer activity of the endoplasmic reticulum (ER)-resident ORP5 and ORP8 is regulated by both PM PI4P and PI(4,5)P2 Dynamic control of ORP5/8 recruitment to the PM occurs through interactions with the N-terminal Pleckstrin homology domains and adjacent basic residues of ORP5/8 with both PI4P and PI(4,5)P2 Although ORP5 activity requires normal levels of these inositides, ORP8 is called on only when PI(4,5)P2 levels are increased. Regulation of the ORP5/8 attachment to the PM by both phosphoinositides provides a powerful means to determine the relative flux of PI4P toward the ER for PS transport and Sac1-mediated dephosphorylation and PIP 5-kinase-mediated conversion to PI(4,5)P2 Using this rheostat, cells can maintain PI(4,5)P2 levels by adjusting the availability of PI4P in the PM.
- MeSH
- biologický transport MeSH
- buněčná membrána metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- fosfatidylinositol-4,5-difosfát metabolismus MeSH
- fosfatidylinositolfosfáty metabolismus MeSH
- fosfatidylseriny metabolismus MeSH
- fosfotransferasy s alkoholovou skupinou jako akceptorem metabolismus MeSH
- HEK293 buňky MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- proteinové domény MeSH
- steroidní receptory chemie metabolismus MeSH
- substrátová specifita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
BACKGROUND: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy. METHODS: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis. RESULTS: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%). CONCLUSIONS: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.
- MeSH
- hodnocení rizik metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- multiparametrická magnetická rezonance * metody MeSH
- nádory prostaty * patologie diagnostické zobrazování diagnóza krev MeSH
- prostata patologie diagnostické zobrazování MeSH
- prostatický specifický antigen * krev MeSH
- retrospektivní studie MeSH
- ROC křivka MeSH
- senioři MeSH
- stupeň nádoru MeSH
- ultrazvukem navigovaná biopsie metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH