19/Wpływ wypełnienia pęcherza moczowego na położenie prostaty i konsekwencje kliniczne dla efektów leczenia promieniowaniem jonizującym chorych na raka gruczołu krokowego

Cel pracyCelem pracy było zbadanie wpływu wypełnienia pęcherza moczowego na położenie gruczołu krokowego oraz konsekwencji klinicznych dla wyników leczenia promieniowaniem jonizującym.MateriałBadaniu poddano 7 pacjentów z rakiem prostaty (T2N0M0) leczonych radykalnie promieniami jonizującymi techniką IMRT w Centrum Onkologii w Bydgoszczy.MetodaWszystkim pacjentom wykonano CT w pozycji terapeutycznej od poziomu S1 do guzów kulszowych oraz NMR dwukrotnie, z pustym pęcherzem i po 30 min. od wypicia 500 ml wody (przekroje poprzeczne, co 3 mm). Dane przesłano do systemu planowania leczenia Eclipse 7,1.67. Dokonano fuzji obrazów NMR z CT. Następnie okonturowano obszary CTV, PTV i narządy krytyczne (odbytnice, pęcherz moczowy) dla różnego stopnia wypełnienia pęcherza. CTV zawierało prostatę z proksymalnym 1 cm odcinkiem pęcherzyków nasiennych. PTV utworzono poprzez dodanie 1 cm marginesu do CTV (wyznaczonego dla pustego pęcherza), za wyjątkiem marginesu od strony odbytnicy, który wynosił 6 mm. Dla każdego pacjenta zaplanowano terapię promieniowania X 15 MV techniką IMRT z 5 pól, za objętość tarczową przyjmując obszar PTV wyznaczony dla pustego pęcherza moczowego. Planowana dawka całkowita wynosiła 74 Gy. Obserwowano wpływ stopnia wypełnienia pęcherzana zmianę położenia gruczołu krokowego w stosunku do pierwotnie zaplanowanego obszaru.WynikiZaobserwowano przesunięcie obszaru CTV w zależności od stopnia wypełnienia pęcherza moczowego. Średnie przesunięcie w osi LAT wynosiło 0.5 mm przy maksymalnym przesunięciu równym 3.5 mm. W osi AP średnie przesunięcie wynosiło 1.4 mm przy maksymalnej wartości 5.5 mm. Dla osi wzdłużnej pacjenta przesuniecie maksymalne wynosiło 5.9 mm, przy średniej wartości 1.2 mm. Przesunięciom geometrycznym towarzyszyły zmiany rozkładu dawki w obszarze CTV.WnioskiNa podstawie uzyskanych wyników można stwierdzić, że wypełnienie pęcherza moczowego może mieć wpływ na dawkę deponowaną w gruczole krokowym. Koniecznym jest poinformowanie pacjenta o konieczności zachowania stałych warunków napromieniania w zależności od preferencji ośrodka (pusty pęcherz lub 30 min po wypiciu). W radioterapii techniką IMRT chorych z rakiem gruczołu krokowego margines 6 mm od strony odbytnicy może wydawać się za mały, jeżeli nie będą zachowane stałe warunki napromieniania. Może to spowodować podanie mniejszej dawki niż pierwotnie zaplanowana w części PTV

Harnessing ion-binding sites for GPCR pharmacology

Endogenous ions play important roles in the function and pharmacology of G-protein coupled receptors (GPCRs). Historically the evidence for ionic modulation ofGPCRfunction dates to 1973 with studies of opioid receptors, where it was demonstrated that physiologic concentrations of sodium allosterically attenuated agonist binding. This Na+-selective effect was distinct from effects of other monovalent and divalent cations, with the latter usually counteracting sodium’s negative allosteric modulation of binding. Since then, numerous studies documenting the effects of mono- and divalent ions on GPCR function have been published. While ions can act selectively and nonselectively at many sites in different receptors, the discovery of the conserved sodium ion site in class A GPCR structures in 2012 revealed the unique nature of Na+ site, which has emerged as a near-universal site for allosteric modulation of class A GPCR structure and function. In this review, we synthesize and highlight recent advances in the functional, biophysical, and structural characterization of ions bound to GPCRs. Taken together, these findings provide a molecular understanding of the unique roles of Na+ and other ions as GPCR allosteric modulators. Wewill also discuss how this knowledge can be applied to the redesign of receptors and ligand probes for desired functional and pharmacological profiles. © 2019, American Society for Pharmacology and Experimental Therapy. All rights reserved

The Interplay Between Post-Critical Beliefs and Anxiety: An Exploratory Study in a Polish Sample

The present research investigates the relationship between anxiety and the religiosity dimensions that Wulff (Psychology of religion: classic and contemporary views, Wiley, New York, 1991; Psychology of religion. Classic and contemporary views, Wiley, New York, 1997; Psychologia religii. Klasyczna i współczesna, Wydawnictwo Szkolne i Pedagogiczne, Warszawa, 1999) described as Exclusion vs. Inclusion of Transcendence and Literal vs. Symbolic. The researchers used the Post-Critical Belief scale (Hutsebaut in J Empir Theol 9(2):48–66, 1996; J Empir Theol 10(1):39–54, 1997) to measure Wulff’s religiosity dimensions and the IPAT scale (Krug et al. 1967) to measure anxiety. Results from an adult sample (N = 83) suggest that three dimensions show significant relations with anxiety. Orthodoxy correlated negatively with suspiciousness (L) and positively with guilt proneness (O) factor—in the whole sample. Among women, Historical Relativism negatively correlated with suspiciousness (L), lack of integration (Q3), general anxiety and covert anxiety. Among men, Historical Relativism positively correlated with tension (Q4) and emotional instability (C), general anxiety, covert anxiety and overt anxiety. External Critique was correlated with suspiciousness (L) by men

Awards, Archives, and Affects: Tropes in the World Press Photo Contest 2009 - 2011

__Abstract__ Photography contests have assumed an increasingly significant public role in the context of the global surge of mass-mediated war reporting. This study focuses on the recurrence of visual tropes in press photographs awarded in the annual contest World Press Photo (WPP) in the years 2009–11. By tropes, we mean conventions (e.g. a mourning woman, a civilian facing soldiers, a distressed witness to an atrocity) that remain unchanged despite their travels across the visual sphere, gaining professional and public recognition and having a strong affective impact. We contend that photography contests such as the WPP influence and organize a process of generic understanding of war, disaster and atrocity that is based on a number of persistent tropes, such as the mourner, the protester or the survivor amidst chaos and ruins. We further show that these tropes are gendered along traditional conceptions of femininity and masculinity, appealing strongly to both judges and wider audiences. The evidence for our claim comes from an analysis of the photographs that won awards, observation of the judging sessions, semi-structured interviews with three jury chairmen, and public commentary on the juries’ choices (blogs, newspapers and websites)

Inhibition of CD40-TRAF6 interactions by the small molecule inhibitor 6877002 reduces neuroinflammation

Background: The influx of leukocytes into the central nervous system (CNS) is a key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across the blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells to induce inflammation and leukocyte trafficking, we explored the hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate neuro-inflammation. Methods: Human monocytes were treated with a small molecule inhibitor (SMI) of CD40-TRAF6 interactions (6877002), and migration capacity across human brain endothelial cells was measured. To test the therapeutic potential of the CD40-TRAF6-blocking SMI under neuro-inflammatory conditions in vivo, Lewis rats and C57BL/6J mice were subjected to acute experimental autoimmune encephalomyelitis (EAE) and treated with SMI 6877002 for 6 days (rats) or 3 weeks (mice). Results: We here show that a SMI of CD40-TRAF6 interactions (6877002) strongly and dose-dependently reduces trans-endothelial migration of human monocytes. Moreover, upon SMI treatment, monocytes displayed a decreased production of ROS, tumor necrosis factor (TNF), and interleukin (IL)-6, whereas the production of the anti-inflammatory cytokine IL-10 was increased. Disease severity of EAE was reduced upon SMI treatment in rats, but not in mice. However, a significant reduction in monocyte-derived macrophages, but not in T cells, that had infiltrated the CNS was eminent in both models. Conclusions: Together, our results indicate that SMI-mediated inhibition of the CD40-TRAF6 pathway skews human monocytes towards anti-inflammatory cells with reduced trans-endothelial migration capacity, and is able to reduce CNS-infiltrated monocyte-derived macrophages during neuro-inflammation, but minimally ameliorates EAE disease severity. We therefore conclude that SMI-mediated inhibition of the CD40-TRAF6 pathway may represent a beneficial treatment strategy to reduce monocyte recruitment and macrophage activation in the CNS and has the potential to be used as a co-treatment to combat MS

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold