BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.
- MeSH
- Electroencephalography MeSH
- Epilepsies, Partial * diagnostic imaging surgery MeSH
- Epilepsy, Temporal Lobe * surgery MeSH
- Epilepsy * diagnostic imaging surgery MeSH
- Cohort Studies MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Retrospective Studies MeSH
- Treatment Outcome MeSH
- Seizures MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
Guanine radical cation (G•+) is a key intermediate in many oxidative processes occurring in nucleic acids. Here, by combining mixed Quantum Mechanical/Molecular Mechanics calculations and Molecular Dynamics (MD) simulations, we study how the structural behaviour of a tract GGG(TTAGGG)3 (hereafter Tel21) of the human telomeric sequence, folded in an antiparallel quadruple helix, changes when one of the G bases is ionized to G•+ (Tel21+). Once assessed that the electron-hole is localized on a single G, we perform MD simulations of twelve Tel21+ systems, differing in the position of G•+ in the sequence. When G•+ is located in the tetrad adjacent to the diagonal loop, we observe substantial structural rearrangements, which can decrease the electrostatic repulsion with the inner Na+ ions and increase the solvent exposed surface of G•+. Analysis of solvation patterns of G•+ provides new insights on the main reactions of G•+, i.e. the deprotonation at two different sites and hydration at the C8 atom, the first steps of the processes producing 8oxo-Guanine. We suggest the main structural determinants of the relative reactivity of each position and our conclusions, consistent with the available experimental trends, can help rationalizing the reactivity of other G-quadruplex topologies.
- MeSH
- DNA chemistry MeSH
- G-Quadruplexes * MeSH
- Guanine chemistry MeSH
- Ions chemistry MeSH
- Nucleic Acid Conformation MeSH
- Quantum Theory * MeSH
- Humans MeSH
- Models, Molecular MeSH
- Oxidative Stress * MeSH
- Solubility MeSH
- Molecular Dynamics Simulation * MeSH
- Telomere chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Differentiation is a central aspect of the parasite life cycle and encompasses adaptation to both host and environment. If we accept that evolution cannot anticipate an organism's needs as it enters a new environment, how do parasite differentiation pathways arise? The transition between vertebrate and insect stage African trypanosomes is probably one of the better studied and involves a cell-cycle arrested or 'stumpy' form that activates metabolic pathways advantageous to the parasite in the insect host. However, a range of stimuli and stress conditions can trigger similar changes, leading to formation of stumpy-like cellular states. We propose that the origin and optimisation of this differentiation program represents repurposing of a generic stress response to gain considerable gain-of-fitness associated with parasite transmission.
Acetylcholinesterase (AChE) is the key enzyme responsible for deactivating the ACh neurotransmitter. Irreversible or prolonged inhibition of AChE, therefore, elevates synaptic ACh leading to serious central and peripheral adverse effects which fall under the cholinergic syndrome spectra. To combat the toxic effects of some AChEI, such as organophosphorus (OP) nerve agents, many compounds with reactivator effects have been developed. Within the most outstanding reactivators, the substances denominated oximes stand out, showing good performance for reactivating AChE and restoring the normal synaptic acetylcholine (ACh) levels. This review was developed with the purpose of covering the new advances in AChE reactivation. Over the past years, researchers worldwide have made efforts to identify and develop novel active molecules. These researches have been moving farther into the search for novel agents that possess better effectiveness of reactivation and broad-spectrum reactivation against diverse OP agents. In addition, the discovery of ways to restore AChE in the aged form is also of great importance. This review will allow us to evaluate the major advances made in the discovery of new acetylcholinesterase reactivators by reviewing all patents published between 2016 and 2019. This is an important step in continuing this remarkable research so that new studies can begin.
- MeSH
- Acetylcholinesterase metabolism MeSH
- GPI-Linked Proteins metabolism MeSH
- Humans MeSH
- Oximes chemistry therapeutic use MeSH
- Patents as Topic MeSH
- Cholinesterase Reactivators * chemistry therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Endometrial cells undergo very specific changes associated with reproductive processes. Cells prepare for embryo development by increasing their volume. Then, if fertilization fails, endometrial cells are liable for apoptosis, preparing new cells that are ready for subsequent processes related to the possibility of embryo implantation and the development of pregnancy. PTX3 and TNFAIP6 are absent or reduced in cultured COCs, resulting in a functional change in COC in vitro. In this work, we want to check how PTX3, HAS2 and TNFAIP6 behave in luminal epithelium primary cell culture. Cells obtained during slaughter from porcine specimens were cultured primarily in vitro for 7 days. Their proliferation patterns were then analysed using RTCA, with the expression of genes of interest evaluated with the use of immunofluorescence and RT-qPCR. The results of these changes in the expression of the genes of interest were analysed on each of the seven days of the porcine luminal primary cell culture. Our study showed the increased level of PTX3, HAS2 and TN¬FAIP6 expression at the same hours of primary culture. Rt-qPCR showed a higher level of expression of the PTX3 gene in the first 72 h, at the end of the lag phase (in the phase of stasis in which the cells adapt to the new environment and often die). In contrast, TNFAIP6 expression increases about 96 hours when the cells are in the full log phase (logarithmic phase growth) and continue this trend in the plateau phase. We did not observe such drastic changes in the HAS2 expression pattern, which leads us to hypothesize that PTX3 and TNFAIP6 are designed to maintain a constant level of HAS2 in the cell throughout its lifetime. The obtained results could become a point of reference for further in vivo and clinical research.
- MeSH
- C-Reactive Protein genetics MeSH
- Endometrium cytology MeSH
- Epithelial Cells cytology MeSH
- Hyaluronan Synthases genetics MeSH
- Cell Adhesion Molecules genetics MeSH
- Swine MeSH
- Primary Cell Culture MeSH
- Cell Proliferation MeSH
- Serum Amyloid P-Component genetics MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Úvod: Leak po ezofagektomii se vyskytuje v 1-30 % případů a je důležitým faktorem pooperační morbidity a mortality s podílem na 40 % pooperačních úmrtí. Endoskopická vakuová terapie (EVAC) je vedle terapie stenty, klipy a chirurgické terapie novou endoskopickou terapeutickou možností. Kazuistika: 72letá polymorbidní pacientka s adenokarcinomem distálního jícnu Siewert II (T1b, N0, M0) byla indikována k resekci horní části žaludku a dolního hrudního jícnu z laparotomie a torakotomie s rekonstrukcí 2staplerovou ezofagogastroanastomózou. 12. pooperační den byl na CT prokázán leak 3. stupně s propagací do pravé pleurální dutiny. Při endoskopii byl nalezen defekt zaujímající 30 % cirkumference, s dutinou o velikosti 7x3x3 cm. Vzhledem k morfologii úniku bylo rozhodnuto o založení EVAC. Léčba EVAC byla použita ve 12 sezeních s 3 až 4denními odstupy v celkové délce trvání 40 dní. Celkem bylo indikováno 5 extraluminálních a 7 intraluminálních aplikací s podtlakem 100-125 mmHg. Stav byl komplikován globálním respiračním selháním pro těžkou pneumonii. Arteficiální ventilace byla ukončena 58. pooperační den. Pacientka byla propuštěna do rehabilitačního zařízení 90. pooperační den. Kontrola 3 měsíce po dimisi potvrzovala uspokojivé funkční výsledky s plnou realimentací. Závěr: Terapie komplikací nitrohrudních anastomóz po ezofagektomii směřuje k redukci invazivity a větší implementaci endoskopických metod. Použití EVAC je přes své nedostatky spojené s nutností opakované aplikace bezpečnou a vysoce účinnou léčebnou alternativou i u rozsáhlých defektů anastomózy. Její další využití, indikace a poměr k dalším léčebným metodám vyžadují další studium.
Introduction: Post-oesophagectomy leakage occurs in 1-30% of cases as a significant factor in postoperative morbidity and mortality, accounting for 40% of postoperative deaths. Endoscopic vacuum therapy (EVAC) is, besides stent therapy, clips and surgical therapy, a new endoscopic therapeutic modality. Case report: A 72-year-old polymorbid female patient with Siewert type II adenocarcinoma of the distal esophagus (T1b, N0, M0) was indicated for resection of the upper stomach and lower thoracic esophagus from laparotomy and thoracotomy with reconstruction using double-stapling anastomosis. On postoperative day 12, a 3rd degree leakage with propagation into the right pleural cavity was proven on CT. Endoscopy showed a defect affecting 30% of the circumference with a 7x3x3 cm cavity. Because of the leak morphology, EVAC was indicated. The therapy comprised 12 sessions with 3-4-day intervals for a total duration of 40 days with 5 extraluminal and 7 intraluminal applications and negative pressure of 100-125 mmHg. The condition was complicated by global respiratory failure due to severe pneumonia. Artificial ventilation was terminated on the 58th postoperative day. The patient was discharged to a rehabilitation facility on the 90th postoperative day. The follow-up 3 months after discharge confirms satisfactory performance results with full replenishment. Conclusion: The therapy of complications of intrathoracic anastomoses after oesophagectomy has shown a trend toward reduced invasiveness and wider implementation of endoscopic methods. In spite of its shortcomings, the use of EVAC is a safe and highly effective therapeutic option even for extensive anastomotic defects. The future use, indications as well as relation to other therapeutic options require further evaluation.
- MeSH
- C-Reactive Protein analysis MeSH
- Digestive System Surgical Procedures methods MeSH
- Esophagectomy * MeSH
- Gastroesophageal Reflux diagnosis etiology MeSH
- Gastroscopy methods MeSH
- Laparotomy methods MeSH
- Humans MeSH
- Esophageal Neoplasms * diagnosis surgery MeSH
- Anastomotic Leak * therapy MeSH
- Postoperative Complications MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
The paper is motivated by severe concerns regarding currently applied care of the pregnancy-associated breast cancer (PABC) characterised by particularly poor outcomes of the disease. Psychological and ethical aspects play a crucial role in PABC: the highest priority not to damage the foetus significantly complicates any treatment generally, and it is quite usual that patients disclaim undergoing any breast cancer treatment during pregnancy. Although, due to global demographic trends, PABC is far from appearing rarely now, severe societal and economic consequences of the disease are still neglected by currently applied reactive medical approach. These actualities require creating new strategies which should be better adapted to the needs of the society at large by advancing the PABC care based on predictive diagnostic approaches specifically in premenopausal women, innovative screening programmes focused on young female populations, targeted prevention in high-risk groups, and optimised treatment concepts. The article summarises the facts and provides recommendations to advance the field-related research and medical services specifically dedicated to the PABC care.
- Publication type
- Journal Article MeSH
- Review MeSH
Technika se začíná stále více prosazovat v léčbě pacientů se všemi typy diabetu. Moderní technika může být nápomocna zejména na poli selfmonitoringu, dávkování inzulinu a zajištění pacientovy bezpečnosti (prevence vzniku těžké hypoglykemie). Může být ale velmi přínosná například i pro sledování nutričního příjmu či fyzické aktivity. V moderním managementu diabetu jsou stále více využívány mobilní telefony, které mohou sloužit například jako přijímače dat z kontinuální monitorace koncentrace glukózy a je na nich možné s využitím příslušných aplikací provádět i analýzu získaných dat. Z hlediska přenosu dat se stále více prosazují tzv. bezdrátové technologie. V článku jsou rozebírány u nás dostupné novinky ve výše zmíněných oblastech, tj. oblast léčby inzulinovou pumpou a glykemického selfmonitoringu.
Technique is more and more employed in a management of patients treated for all diabetes types. Modern technical approach is particularly helpful in following areas: selfmonitoring, insulin delivery and patient´s safety (prevention of serious hypoglycaemia occurrence) but can be helpful in the monitoring of nutritional intake or physical activity as well. There is a trend to use smart phones in diabetes management for example as receivers for continuous glucose monitoring. By using mobile applications (which can be installed into smartphones) patient´s data analysis can be provided too. Modern devices are constructed nowadays to use preferentially wireless technology. In this article innovations, currently available in the Czech Republic for insulin pump treatment and glycaemic selfmonitoring are discussed.
- Keywords
- kontinuální monitorace koncentrace glukózy,
- MeSH
- Wireless Technology MeSH
- Patient Safety MeSH
- Diabetes Mellitus * diagnosis drug therapy MeSH
- Hypoglycemia prevention & control MeSH
- Data Interpretation, Statistical MeSH
- Insulin Infusion Systems * trends MeSH
- Blood Glucose analysis MeSH
- Humans MeSH
- Cell Phone utilization MeSH
- Blood Glucose Self-Monitoring * instrumentation trends MeSH
- Software MeSH
- Telemedicine instrumentation utilization MeSH
- Computer Security MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
... 54 Cellular Injury, 54 General Mechanisms of Cell Injury, 55 Hypoxic Injury, 56 Free Radicals and Reactive ... ... Circulation, 389 Selective Adherence in Favorable Sites, 389 Escape from the Circulation and Development of a New ... ... McCance -- Genetics, Epigenetics, and Tissue, 403 Incidence and Mortality Trends, 409 Incidence Trends ... ... , 409 Mortality Trends, 410 In Utero and Early Life Conditions, 410 Environmental-Lifestyle Factors, ...
7th ed. xxvi, 1810 s. : il. (převážně barev.) ; 29 cm
- MeSH
- Biomedical Research MeSH
- Child MeSH
- Adult MeSH
- Physiology MeSH
- Clinical Medicine MeSH
- Pathology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Conspectus
- Experimentální medicína
- Učební osnovy. Vyučovací předměty. Učebnice
- NML Fields
- patologie
- fyziologie
- NML Publication type
- učebnice vysokých škol
- kolektivní monografie
Doporučené postupy pro léčbu hyperglykemie při diabetu 2. typu orientují péči na pacienta. Léčba by měla minimalizovat nežádoucí účinky terapie a snižovat riziko vzniku cévních komplikací. Nejzávažnějším rizikem antidiabetické terapie je vznik hypoglykemických příhod. Obava z hypoglykemické příhody je i bariérou efektivní terapie diabetu. Diabetes mellitus je progredující onemocnění, které vyžaduje aktivní změnu léčby dle vývoje k dosažení individuálních cílů kompenzace. Nejnižší rizika hypoglykemických příhod má terapie metforminem, inhibitory dipeptidylpetidázy IV, receptorovými agonisty GLP-1 a inzulinovými analogy. Nově se dostávají do terapie diabetu glifloziny a perspektivní se jeví i glitazary, které aktivují PPAR receptory. Individualizovaná terapie vyžaduje i úzkou spolupráci s pacientem k dosažení vzájemné shody v léčebném postupu.
Recommended steps for treatment of hyperglycemia during the type 2 diabetes are orientated towards patients. Medical treatment should minimalize undesirable effects of therapy and decrease the danger of rising of vascular complications. The most serious danger consequent upon diabetes therapy is commencement of hypoglycemia accidents. One of the obstacles of effective therapy of diabetes is caused by worries of hypoglycemia accident. Diabetes mellitus is developing disease, which needs active change of treatment, which depend on progress to achieve individual aims of control. The lowest possibility of hyporglycemia accidents contained therapy by metformin, DPP-4 inhibitors, GLP-1 agonists and insulin analogues. Glifloziny recently participate in therapy of diabetes and also glitazary, which activate PPAR receptors, seem perspective. Individual therapy requires close cooperation with patient to achieve mutual agreement regarding method of medical treatment.
- Keywords
- individualizovaná terapie,
- MeSH
- Diabetes Mellitus, Type 2 * drug therapy MeSH
- Glucagon-Like Peptide 1 agonists pharmacology therapeutic use MeSH
- Hypoglycemia prevention & control MeSH
- Hypoglycemic Agents * adverse effects therapeutic use MeSH
- Dipeptidyl-Peptidase IV Inhibitors therapeutic use MeSH
- Incretins pharmacology therapeutic use MeSH
- Insulin therapeutic use MeSH
- Drug Therapy, Combination * methods MeSH
- Humans MeSH
- Metformin therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
