To design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients.
...For 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-range of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix–uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix–uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated.
The margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% ± 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and −1% to 9%; p < 0.004) and the CTV-to-PTV volume (4–96 ml).
Compared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.
Gaucher and Fabry diseases are the most prevalent sphingolipidoses. Chronic inflammation is activated in those disorders, which could play a role in pathogenesis. Significant degrees of amelioration ...occur in patients upon introduction of specific therapies; however, restoration to complete health status is not always achieved. The idea of an adjunctive therapy that targets inflammation may be a suitable option for patients. PPS is a mixture of semisynthetic sulfated polyanions that have been shown to have anti-inflammatory effects in mucopolysaccharidosis type I and II patients and animal models of type I, IIIA and VI. We hypothesized PPS could be a useful adjunctive therapy to inflammation for Gaucher and Fabry diseases. The objective of this work is to analyze the in vitro effect of PPS on inflammatory cytokines in cellular models of Gaucher and Fabry diseases, and to study its effect in Gaucher disease associated in vitro bone alterations. Cultures of peripheral blood mononuclear cells from Fabry and Gaucher patients were exposed to PPS. The secretion of proinflammatory cytokines was significantly reduced. Peripheral blood cells exposed to PPS from Gaucher patients revealed a reduced tendency to differentiate to osteoclasts. Osteoblasts and osteocytes cell lines were incubated with an inhibitor of glucocerebrosidase, and conditioned media was harvested in order to analyze if those cells secrete factors that induce osteoclastogenesis. Conditioned media from this cell cultures exposed to PPS produced lower numbers of osteoclasts. We could demonstrate PPS is an effective molecule to reduce the production of proinflammatory cytokines in in vitro models of Fabry and Gaucher diseases. Moreover, it was effective at ameliorating bone alterations of in vitro models of Gaucher disease. These results serve as preclinical supportive data to start clinical trials in human patients to analyze the effect of PPS as a potential adjunctive therapy for Fabry and Gaucher diseases.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the article the author analyzes ownership and contribution notes notes published in Ukrainian catalogs of Cyrillic old printed editions, which are original and indigenous objects of local studies. ...Such notes contain information about contributions and contributors, their families’ members, priests, landed estates’ owners, about the other gifts, temples building and renovation, founders and beneficiaries, about military expeditions, battles, natural phenomena. Sometimes the notes include titles of several books given to a temple or list other religious items. Notes related to the history and local studies make it possible to reconstruct some episodes of the history of Ukrainian local territories, towns, villages, communities, churches and monasteries
The main premise for the emergence of the concept of low-opioid general anesthesia was the phenomenon of the formation of drug/opioid dependence in patients undergoing surgery under multicomponent ...anesthesia with high doses of narcotic analgesics (opioids). Opioids were used as the main analgesics and in the postoperative period. The above factors contributed to the development of opiate addiction in operated patients in the late postoperative period. The mass nature of this phenomenon has become one of the most urgent problems in modern anesthesiology.
Our study aimed to evaluate the antinociceptive/antistress efficacy of 3 types of low-opioid multimodal general anesthesia in laparoscopic renal surgery.
Methods. Eighty patients who had undergone laparoscopic renal surgery under 3 types of general anesthesia were included in this prospective cohort study. All patients were operated under general anesthesia with tracheal intubation. Induction: intravenous (IV) propofol 2 mg/kg, fentanyl 1.5-2 μg/kg, atracurium 0.6 mg/kg. Maintenance of anesthesia: sevoflurane (MAC - 1.44±0.25% by volume). In group 1 (control group n = 26), analgesia was provided with fentanyl 3,89±2.03 μg/kg/h. In group 2 (n = 25), multimodal low-opioid general anesthesia was performed with fentanyl 1.76±1.2 μg/kg/h and IV lidocaine 1.5 mg/kg/h and subanesthetic doses of ketamine. In group 3 (n = 29), multimodal anesthesia with low opioids was performed with fentanyl 2.38±1.01 μg/kg/h in combination with dexmedetomidine 0.7 μg/kg/h. The efficacy of antinociceptive protection was assessed by the dynamics of changes in stress hormone levels, hemodynamic parameters, and blood glucose concentration.
Results. The mean total dose of fentanyl used throughout the anesthetic period was: 369,23±83,75 μg in group 1, 216,0±47,26 μg in group 2, and 272,41±58,14 μg in group 3 (p < 0.001). Mean cortisol levels were significantly different before and after surgery in groups 1 and 2: 371,0±161,61 nmol/l vs 562,72±226,87 nmol/l (p < 0.01) and 531,08±218,02 nmol/l vs 831,33±235,32 nmol/l (p < 0.01), respectively. In group 3, we did not detect any statistical difference: 393,51±134,69 nmol/l and 436,37±188,09 nmol/l, respectively (p > 0.05). The mean level of adrenocorticotropic hormone increased significantly after surgery in all studied groups: 111.86% in group 1 (p < 0.01), 122.02% (p < 0.01) in group 2 and 78.59% (p < 0.01) in group 3. Blood glucose levels in the postoperative (p/o) period did not exceed 6,16±1,67 mmol/l (p > 0.05) in all groups. Hemodynamic parameters and BIS, which were maintained within 44±6.4%, indicated the adequacy of anesthesia and analgesia in the study groups.
In group 1, 8 of 26 patients required additional analgesia with opioids during the p/o period (pain intensity on the VAS scale exceeded 4 points). In group 2 and group 3, 4 patients each required opioid analgesia, 16% and 15.38%, respectively. The next day after surgery, all patients were mobilized (sitting in bed, walking). Markers of renal function were also within normal range in all patients.
Conclusion. The use of low-opioid multimodal anesthesia with IV lidocaine or dexmedetomidine during laparoscopic renal surgery provides an adequate anesthetic/antinociceptive effect. The use of dexmedetomidine in multimodal general anesthesia provides the greatest antinociceptive protection and reduces the stress response to surgery.
Physical macroporous poly(vinyl alcohol)-based cryogels formed by the freeze-thaw technique without the use of any foreign cross-linkers are of significant interests for biomedical applications. In ...the present study, such gel materials loaded with the antimicrobial substances were prepared and their physicochemical properties were evaluated followed by an assessment of their potential to serve as drug carriers that can be used as implants for the treatment of infected wounds. The antibiotic Ceftriaxone and the antimycotic Fluconazole were used as antimicrobial agents. It was shown that the Ceftriaxone additives caused the up-swelling effects with respect to the cryogel matrix and some decrease in its heat endurance but did not result in a substantial change in the gel strength. With that, the drug release from the cryogel vehicle occurred without any diffusion restrictions, which was demonstrated by both the spectrophotometric recording and the microbiological agar diffusion technique. In turn, the in vivo biotesting of such drug-loaded cryogels also showed that these materials were able to function as rather efficient antimicrobial implants injected in the artificially infected model wounds of laboratory rabbits. These results confirmed the promising biomedical potential of similar implants.
In addition to their use as colorants in food and cosmetics, various natural dyes possess photophysical properties that could enable their use as modular building blocks for preparing eco-friendly ...and non-toxic chromophores. Among the natural pigments, guaiazulene holds great potential due to its unique optical and electronic properties. Thus, in order to explore and understand the properties of guaiazulene-containing chromophores, a series of 4-styrylguaiazulenes
3a–l
were prepared by condensation of the C-4 methyl group of naturally-occurring guaiazulene
1
with various aromatic carboxaldehydes
2a–l
. Treatment of these analogs
3a–l
with a strong acid protonates the electron-rich C-3 position and reveals a reversible halochromic behavior where the optical energy gap responds predictably to the electron-donor strength and the degree of π-conjugation. Additionally, acid-doping is accompanied by efficient fluorescence switch-on, where
3e
(H
+
) and
3g
(H
+
) exhibited considerably higher fluorescence quantum yields than the neutral precursor. These properties facilitated the design of a new non-erasable 3D fluorescence readout (permanent or write-once read-many, WORM) system, which is comprised of a switch-on fluorescent guaiazulene-containing chromophore
3e
and a commercially available iodonium photo-acid generator (PAG) in thin polymethyl methacrylate (PMMA) films.
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•Residues of red seaweed Gelidium after phycocolloid extraction still contain 44 % of upgradable carbohydrates.•Hydrolysis of Gelidium cabohydrates to monosaccharides yielded 30 % ...(w/w) glucose per g dry biomass.•Hydrolysates from Gelidium residues are suitable C-sources for P3HB production by Halomonas boliviensis.•Halomonas boliviensis accumulated 41 % (w/w) of P3HB based on the algal hydrolysates.•The outlined process adds value to waste seaweed and promotes circular economy.
Agar extraction from Gelidium and Gracilaria red seaweed species produces hundred thousand ton of carbohydrate-rich residues annually. Gelidium sesquipedale waste biomass obtained after agar extraction, still contained 44.2 % w/w total carbohydrates (dry-weight basis). These residues were biologically up-graded to poly-3-hydroxybutyrate (P3HB) after saccharification of their carbohydrate fraction to simple sugars. A combined hydrolysis treatment using sulfamic acid followed by enzymatic hydrolysis with cellulases produced a glucose-rich hydrolysate with a negligible content of inhibitors. With this treatment a sugar yield of circa 30 % (g glucose/g biomass) was attained. The algal hydrolysates were assessed as carbon source for the production of P3HB by the halotolerant bacteria Halomonas boliviensis. A cell concentration of 8.3 g L−1 containing 41 % (w/w) of polymer and a yield (YP/S) of 0.16 gpolymer/gglucose were attained in shake flask assays. In this work, cellulose-rich seaweed waste was shown to be an upgradable, sustainable source of carbohydrates.
The paper presents a new monitoring station DIAMIS for continuous precisious observations of atmospheric carbon dioxide (CO
2
) and methane (CH
4
) mole fractions over the Yenisei Gulf, on the ...southwestern coast of the Taimyr Peninsula at the edge of the Dikson settlement. Here, we summarize technical details of the instrumental setup, give an overview of calibration and data processing algorithms, describe local environments of the study area, and analyze the seasonal footprint of the measurement station. Based on the observations in September 2018–February 2020, a comparative analysis of the atmospheric CO
2
and CH
4
annual variations in the polar belt (DIAMIS) and middle-taiga subzone (ZOTTO observatory) of near-Yenisei Siberia is presented.
A comprehensive investigation of the electronic structure and fast relaxation processes in the excited states of new styryl base-type derivatives was performed using steady-state, pico-, and ...femtosecond time-resolved spectroscopic techniques. Linear photophysical parameters of new compounds, including steady-state absorption, fluorescence, and excitation anisotropy spectra, were obtained in a number of organic solvents at room temperature. A detailed analysis of the fluorescence lifetimes and ultrafast relaxation processes in the electronically excited state of the styryl bases revealed an important role of solvate dynamics and donor–acceptor strength of the molecular structures in the formation of their excited state absorption spectra. Experimental data were in good agreement with quantum chemical calculations at the time dependent density functional theory level, combined with a polarizable continuum model.
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