Wpływ systemu wewnątrzmacicznego uwalniającego lewonorgestrel Mirena® (Bayer) na prewencję i leczenie raka gruczołowego błony śluzowej macicy oraz na inne nowotwory złośliwe u kobiet

The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 μg of levonorgestrel daily. Consequently, the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk. To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study, Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrelreleasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.Hormonalne wkładki wewnątrzmaciczne znajdują się w coraz szerszym użyciu od lat 80-tych XX wieku. Istnieją już długoterminowe obserwacje odnośnie następstw medycznych ich stosowania. Celem pracy było dokonanie krótkiego przeglądu piśmiennictwa odnośnie profilaktycznych aspektów wkładki wewnątrzmacicznej uwalniającej lewonorgestrel w odniesieniu do częstości występowania nowotworów złośliwych u kobiet. Taki wpływ jest szczególnie ważny w świetle obserwowanego obecnie wzrostu częstości występowania raków gruczołowych trzonu i szyjki macicy. Na ile są już dostępne niskodawkowe wkładki wewnątrzmaciczne, to twarde dane medyczne odnoszą się zasadniczo do wkładki Mirena® (Bayer), uwalniającej miejscowo średnio od 20 do 14 μg lewonorgestrelu dziennie. Jej działanie ochronne wiąże się ze zmniejszeniem ryzyka zachorowania na raka endometrium aż o 50% względem średniego ryzyka populacyjnego. W mniejszym stopniu zmniejsza ona ryzyko zachorowania na raka gruczołowego i płaskonabłonkowego szyjki macicy, raka jajnika, trzustki oraz oskrzela. W jednym z badań Mirena® podnosiła o około 20% ryzyko wystąpienia raka piersi, podczas gdy w innych badaniach takiego wzrostu ryzyka nie zaobserwowano. Przy coraz częstszym rozpoznawaniu insulinooporności i otyłości w ostatnich dekadach oraz coraz wcześniejszym występowaniu nowotworów hormonozależnych szersze stosowanie systemów wewnątrzmacicznych uwalniających lewonorgestrel może się okazać bardzo istotnym elementem profilaktyki pierwotnej nowotworów złośliwych u kobiet. Dla przykładu, osoby z nadwagą i otyłością wydają się być predystynowane do stosowania takiej interwencji hormonalnej

Brak korelacji stężeń amoniaku i żeńskich hormonów płciowych w ludzkim przedowulacyjnym płynie pęcherzykowym

Objective: The ammonia gradient from the human preovulatory follicular fluid (FF) to blood has been documented. The purpose of the present study was to substantiate whether, following controlled ovarian hyperstimulation, female sex hormones are related to this phenomenon. Material and Methods: Blood was taken from the antecubital veins of 32 randomly selected patients undergoing an in vitro fertilization program prior to oocyte retrieval and FF collection. Ammonia concentrations in blood and FF were determined by the indophenol method, and 17β-estradiol (E2) and progesterone (PGS) concentrations In plasma and FF by radioimmunoassay. Results: The mean ammonia concentration was 39.15 +/-3.25 μM for FF, and 20.15 +/-1.20 μM for blond (pCel: Udokumentowano istnienie gradientu stężeń amoniaku między ludzkim przedowulacyjnym płynem pęcherzykowym (FF) a krwią. Celem niniejszej pracy było ustalenie czy – po kontrolowanej hiperstymulacji jajników – żeńskie hormony płciowe mają związek z tym zjawiskiem. Materiał i metoda: Krew żylną ze zgięcia łokciowego pobrano bezpośrednio przed pozyskaniem oocytu i FF od 32 losowo wybranych pacjentek poddanych procedurze zapłodnienia pozaustrojowego. Stężenia amoniaku we krwi pełnej i w FF zmierzono metodą indofenolową, a stężenia 17β-estradiolu (E2) i progesteronu (PGS) w osoczu i w FF – metodą radioimmunologiczną. Wyniki: Średnie stężenie amoniaku wyniosło 39,15 +/- 3,25 μM w FF, a 20,15 +/-1,20 μM we krwi (p < 0,001). U wszystkich badanych stosunek stężenia amoniaku w FF do stężenia amoniaku we krwi wyniósł powyżej 1,0, co potwierdza produkcję amoniaku przez pęcherzyk przedowulacyjny. Nie stwierdzono istnienia korelacji między stężeniami amoniaku i E2 w FF (współczynnik korelacji rang Spearmana r = 0,2546; p = 0,160), ani między stężeniem amoniaku w FF i różnicą stężeń E2 między FF a osoczem (r = 0,2416; p = 0,183). Podobnie nie wykryto korelacji między stężeniami amoniaku i PGS w FF (r = -0,1089; p = 0,553), co podkreślił brak korelacji między stężeniem amoniaku w FF i różnicą stężeń PGS między FF a osoczem. Wnioski: Produkcja amoniaku nie jest bezpośrednio powiązana z wewnątrzpęcherzykowymi stężeniami żeńskich hormonów płciowych. Natomiast wewnątrzpęcherzykowa akumulacja amoniaku może być odpowiedzialna za zasadowe pH ludzkiego płynu pęcherzykowego

Development of a CFD model for propeller simulation.

The article presents a development of numerical model for a single propeller simulation and comparison of obtained results with experimental data available from a test campaign in scale 1:1. Described simulation is a steady state computation taking advantage of Multiple Reference Frame model implemented in Ansys CFX. The paper includes an analysis of rotating domain thickness influence on numerical values of thrust and power. The results indicate that this type of simulation may be sensitive to the sizing of rotating domain especially when disc solidity is low, or when the number of blades is 2, a frequent situation in all electric flight vehicles. The analysis shows that performing simulations, using one domain sizing, for a number of flight scenarios requiring analysis of a few rotational speeds can produce unintuitive results. Therefore, it is suggested to calibrate the model, preferably by experimental results

Odmienny wpływ agonistów receptorów β2- i β3-adrenergicznych na spontaniczne skurcze myometrium kobiet nieciężarnych

Abstract Objective: This study aimed to compare the relaxant properties of BRL 37344 with β2-adrenoceptors agonist ritodrine on the contractility of human nonpregnant myometrium. Material and methods: The activity of myometrial strips mounted in an organ bath was recorded under isometric conditions using force transducers with digital output. Contractility before and after cumulative additions of both uterorelaxants and with preincubation with β-adrenoceptor antagonists bupranolol, propranolol, and butoxamine were studied. Results: Both BRL 37344 (10-10 – 10-4 mol/L) and ritodrine (10-10 – 10-5 mol/L) decreased the area under curve, or AUC, value (logIC50 -6.45 ± 0.18 and -8.71 ± 0.35, respectively), and the degree of inhibition of spontaneous contractile activity was similar (< 30%). However, BRL 37344 decreased the mean frequency of contractions, whereas ritodrine decreased the mean amplitude of contractions. The inhibition of contractions by BRL 37344 was partially antagonized by bupranolol and propranolol, but not with butoxamine. The inhibition by ritodrine was counteracted by all these antagonists. Conclusions: The effects of BRL37344 and ritodrine on human nonpregnant myometrium are quantitatively similar in respect to the inhibition of spontaneous contractility, yet are also distinct due to their substantially different influences on contraction parameters. Our data indicate that β3-adrenoceptor activation is not the sole effect of BRL 37344 on this tissue.Streszczenie Cel pracy: Niniejsze badanie zaprojektowano celem oceny rozkurczowego działania BRL 37344 w porównaniu do ritodryny (referencyjnego agonisty receptorów β2-adrenergicznych) na spontaniczną czynność skurczową ludzkiego nieciężarnego myometrium. Materiał i metody: Skurcz izolowanych skrawków mięśni gładkich rejestrowano w warunkach izometrycznych przy użyciu cyfrowych przetworników siły. Ocenie poddawano zmiany kurczliwości skrawków podczas kumulacyjnego zwiększania stężeń agonistów bez obecności oraz w obecności antagonistów receptorów β adrenergicznych: bupranololu, propranololu oraz butoksaminy. Wyniki: Inkubacja skrawków myometrium z BRL 37344 (10-10 – 10-4 mol/L) oraz ritodryną (10-10 – 10-5 mol/L) skutkowała porównywalnym

Isoprostanes as potential cerebral vasospasm biomarkers

Despite enormous progress in medicine, symptomatic cerebral vasospasm (CVS), remains an unexplained clinical problem, which leaves both physicians and patients helpless and relying on chance, due to the lack of specific marker indicative of imminent danger as well as the lack of specific treatment. In our opinion CVS occurrence depends on dynamic disbalance between free radicals' formation (oxidative stress) and antioxidant activity. Isoprostanes are products of free-radical peroxidation of polyunsaturated fatty acids, and seem to mark a promising path for the research aiming to unravel its possible mechanism. Not only are they the biomarkers of oxidative stress in vivo and in vitro, but also have manifold biological effects (including vasoactive, inflammatory and mitogenic) via activation of the thromboxane A2 receptor (TBXA2R), both in physiological and pathophysiological processes. This review addresses the importance of isoprostanes in CVS in quest of appropriate biomarkers

Atypical Endometrial Hyperplasia Arising in a Cesarean Section Scar: A Mechanism of Malignant Transformation

The incidence of scar endometriosis in Cesarean sections varies between 0.03 and 0.4%. However, the recently increased rate of Cesarean sections worldwide may be causing an increase in occurrence of scar endometriosis. This report presents anatomopathological evidence of an early-stage malignant transformation in endometriotic tissue from a post-Cesarean scar and briefly reviews possible underlying mechanisms. A 40-year-old woman with a body mass index of 42.7 was referred to the gynecological department with recurrent pain and presence of a palpable mass in her Cesarean section scar. She had undergone this procedure 7 years earlier and began experiencing discomfort and pain at the incision site 6 months postoperatively. Surgical treatment was instituted with complete removal of the lesion. Anatomopathological examination revealed endometriotic tissue intertwined with atypical endometrial hyperplasia and fibrosis. At 2 years’ follow-up, she was asymptomatic, both clinically and based on ultrasound examination. Endometriotic foci inoculated within an abdominal scar may undergo malignant transformation. Long-lasting abdominal scar endometriosis, in morbidly obese women, requires special attention from the physician

The use of a hybrid Sequential Biofiltration System for the improvement of nutrient removal and PCB control in municipal wastewater

This article aims to evaluate the efficiency of an innovative hybrid Sequential Biofiltration System (SBS) for removing phosphorus and nitrogen and polychlorinated biphenyls (PCBs) from original municipal wastewater produced by a Wastewater Treatment Plant under authentic operating conditions. The hybrid SBS was constructed with two barriers, a geochemical (filtration beds with limestone, coal and sawdust) and a biological barrier (wetlands with Glyceria, Acorus, Typha, Phragmites), operating in parallel. Significant differences were found between inflow and outflow from the SBS with regard to wastewater contaminant concentrations, the efficiency of removal being 16% (max. 93%) for Total Phosphorus (TP), 25% (max. 93%) for Soluble Reactive Phosphorus (SRP), 15% (max. 97%) for Total Nitrogen (TN), 17% (max. 98%) for NO3 –N, and 21% for PCB equivalency (PCB EQ). In the case of PCB EQ concentration, the highest efficiency of 43% was obtained using beds with macrophytes. The SBS removed a significant load of TP (0.415 kg), TN (3.136 kg), and PCB EQ (0.223 g) per square meter per year. The use of low-cost hybrid SBSs as a post-treatment step for wastewater treatment was found to be an effective ecohydrological biotechnology that may be used for reducing point source pollution and improving water quality

Re-treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE of patients with progressive neuroendocrine neoplasm

Background: Neuroendocrine neoplasms (NENs) are heterogeneous groups of tumours derived from neuroendocrine cells of the ectoderm or endoderm. They are considered rare, with an estimated incidence and prevalence of 6/100,000 and 35/100,000 respectively, and a noticeable upward trend. Radioligand therapy (RLT) using beta-radiation-emitters combined with somatostatin analogues is an effective and relatively safe treatment method. It is usually used as a second-line therapy in case of progressive disease. Material and methods: In retrospective analysis covering eight years of observation (2015–2023) of patients treated in a single highest-reference NEN centre, a subgroup of 13 who received RLT re-treatment (177Lu or 177Lu/90Y-mixture) was identified. Epidemiological aspects, renal, hepatic, haematological parameters and chromogranin A serum concentration were analysed. Results: The median PFS after the first cycle of RLT was 53.8 months (IQR = 19.3). Directly after the second cycle of RLT disease stabilization and progression was observed in 11/13 (84.6%) and 2/13 (15.4%) patients respectively. After the second cycle of RLT median observation time for the study group was 16.2 months. Eight out of 13 patients were reachable for long-term observation and stabilization was confirmed in 62.5 % (5/8), progression in 12.5% (1/8) and death in 25% (2/8) patients. Median survival time in patients with confirmed death was 7 months. During observation, an increase in creatinine concentration with a decrease in glomerular filtration rate (GFR) was noticed, however, the values were at a statistical trend level (p = 0.056; p = 0.071). The increase of liver parameters was statistically, but not clinically significant. The decrease in albumin concentration and fasting glucose concentration were not significant. An increase in chromogranin A concentration correlated, although not statistically, with the progression of the disease. A statistically significant decrease in the number of all bone marrow cell lines was observed. The first RLT cycle caused a higher decrease in blood parameters than the second. There were no differences in PFS or laboratory parameters depending on the radioligand ([177Lu]Lu-DOTA-TATE vs. [177Lu]Lu-DOTA-TATE/[90Y]Y-DOTA-TATE). Conclusions: In follow-up after RLT re-treatment stabilization was observed in 62.5%, progression in 12.5% and death in 25% of patients. Decrease of glomerular filtration, and bone marrow parameters resulted from the cumulative adverse effect of RLT, the natural ageing process, and the progression of the disease. Side effects were mainly caused by the first treatment cycle. There was no significant influence on the measured parameters, depending on the radioisotope used. Re-treatment of RLT seems to be a reliable and relatively safe method, thus should be considered in patients who underwent one cycle of RLT and responded to the treatment

Digital health and mobile health: a bibliometric analysis of the 100 most cited papers and their contributing authors

Aim: This study aimed to identify and analyze the top 100 most cited digital health and mobile health (m-health) publications. It could aid researchers in the identification of promising new research avenues, additionally supporting the establishment of international scientific collaboration between interdisciplinary research groups with demonstrated achievements in the area of interest. Methods: On 30th August, 2023, the Web of Science Core Collection (WOSCC) electronic database was queried to identify the top 100 most cited digital health papers with a comprehensive search string. From the initial search, 106 papers were identified. After screening for relevance, six papers were excluded, resulting in the final list of the top 100 papers. The basic bibliographic data was directly extracted from WOSCC using its “Analyze” and “Create Citation Report” functions. The complete records of the top 100 papers were downloaded and imported into a bibliometric software called VOSviewer (version 1.6.19) to generate an author keyword map and author collaboration map. Results: The top 100 papers on digital health received a total of 49,653 citations. Over half of them (n = 55) were published during 2013–2017. Among these 100 papers, 59 were original articles, 36 were reviews, 4 were editorial materials, and 1 was a proceeding paper. All papers were written in English. The University of London and the University of California system were the most represented affiliations. The USA and the UK were the most represented countries. The Journal of Medical Internet Research was the most represented journal. Several diseases and health conditions were identified as a focus of these works, including anxiety, depression, diabetes mellitus, cardiovascular diseases, and coronavirus disease 2019 (COVID-19). Conclusions: The findings underscore key areas of focus in the field and prominent contributors, providing a roadmap for future research in digital and m-health