Attitudes and perceptions of affected women towards endocrine endometriosis therapy: an international survey based on free-word association networks

STUDY QUESTION What are the attitudes and perceptions towards endocrine endometriosis therapy? SUMMARY ANSWER Among the study population, endocrine endometriosis therapies are associated with negative mental images and emotions and there seems to be a pre-therapeutic information deficit on the part of physicians. WHAT IS KNOWN ALREADY Endocrine therapies, as the current standard of conservative endometriosis treatment, have good efficacy and improve symptoms and quality of life in most patients. Nevertheless, clinical practice repeatedly shows rejection on the part of patients, which may result in reduced compliance and discontinuation of therapy. STUDY DESIGN, SIZE, DURATION Cross-sectional study among endometriosis patients using a multilingual questionnaire distributed via the most popular social media channels between November 2020 and February 2021. A total of 3348 women participated in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on a pilot phase, an international, multilingual online survey was conducted among women affected by endometriosis. The questionnaire included free-word associations and questions about personal medical history, source of information, and demographic data. Mental representations were detected based on modules of the co-occurrence network of associations. MAIN RESULTS AND THE ROLE OF CHANCE Six modules with different dominant emotional labels emerged from the confluence of associations to endocrine endometriosis therapy mentioned by participants. Five modules reflected negative mental associations, with the most frequently mentioned words being ‘side effects’, ‘pain’, ‘ineffective’, ‘depression’, and ‘uncertainty’. Of the 12 most frequently selected emotions, only ‘optimistic’ was positive. Side effects affecting mental health are the most important reason for deciding against endocrine therapy in our survey population. Twenty-seven percent of respondents reported knowing little about endocrine therapies for endometriosis. Social media are the most frequently used sources of information and were rated as the most useful. LIMITATIONS, REASONS FOR CAUTION By translating the questionnaire, questions might have been understood differently depending on the language. By using social media channels for distribution, digitally literate patients were targeted. The survey population might not be representative as patients who are critical/unhappy with therapy are more likely to seek advice from peer groups. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study replicate the findings of a recent survey in three European countries. Given the prevalence of endometriosis and the few emerging pharmaceutical alternatives, these data point to a growing need for further research and development of non-hormonal drugs for treating endometriosis. Most endometriosis patients are young and digitally literate, and much information is obtained from alternative sources, such as social media. Careful education before starting therapy should be taken seriously, and patients’ concerns should be addressed individually by health care providers. This could help reduce misunderstanding and misinformation and improve treatment adherence and satisfaction. STUDY FUNDING/COMPETING INTEREST(S) There is no funding or conflict of interest to declare. TRIAL REGISTRATION NUMBER The trial is not registered at any trial registry

Reversal of hemochromatosis by apotransferrin in non-transfused and transfused Hbbth3/+ (heterozygous b1/b2 globin gene deletion) mice

Intermediate beta-thalassemia has a broad spectrum of sequelae and affected subjects may require occasional blood transfusions over their lifetime to correct anemia. Iron overload in intermediate beta-thalassemia results from a paradoxical intestinal absorption, iron release from macrophages and hepatocytes, and sporadic transfusions. Pathological iron accumulation in parenchyma is caused by chronic exposure to non-transferrin bound iron in plasma. The iron scavenger and transport protein transferrin is a potential treatment being studied for correction of anemia. However, transferrin may also function to prevent or reduce iron loading of tissues when exposure to non-transferrin bound iron increases. Here we evaluate the effects of apotransferrin administration on tissue iron loading and early tissue pathology in non-transfused and transfused Hbb(th3/+) mice. Mice with the Hbb(th3/+) phenotype have mild to moderate anemia and consistent tissue iron accumulation in the spleen, liver, kidneys and myocardium. Chronic apotransferrin administration resulted in normalization of the anemia. Furthermore, it normalized tissue iron content in the liver, kidney and heart and attenuated early tissue changes in non-transfused Hbb(th3/+) mice. Apotransferrin treatment was also found to attenuate transfusion-mediated increases in plasma non-transferrin bound iron and associated excess tissue iron loading. These therapeutic effects were associated with normalization of transferrin saturation and suppressed plasma non-transferrin bound iron. Apotransferrin treatment modulated a fundamental iron regulatory pathway, as evidenced by decreased erythroid Fam132b gene (erythroferrone) expression, increased liver hepcidin gene expression and plasma hepcidin-25 levels and consequently reduced intestinal ferroportin-1 in apotransferrin-treated thalassemic mice

Moderate lameness leads to marked behavioral changes in dairy cows.

Lameness is one of the most prevalent diseases affecting the welfare of cows in modern dairy production. Lameness leads to behavioral changes in severely lame cows, which have been investigated in much detail. For early detection of lameness, knowledge of the effects of moderate lameness on cow behavior is crucial. Therefore, the behavior of nonlame and moderately lame cows was compared on 17 Swiss dairy farms. On each farm, 5 to 11 nonlame (locomotion score 1 of 5) and 2 to 7 moderately lame (locomotion score 3 of 5) cows were selected for data collection in two 48-h periods (A, B) separated by an interval of 6 to 10 wk. Based on visual locomotion scoring, 142 nonlame and 66 moderately lame cows were examined in period A and 128 nonlame and 53 moderately lame cows in period B. Between these 2 periods, the cows underwent corrective hoof trimming. Lying behavior, locomotor activity, and neck activity were recorded by accelerometers (MSR145 data logger, MSR Electronics GmbH, Seuzach, Switzerland), and feeding and rumination behaviors by noseband sensors (RumiWatch halter, ITIN + HOCH GmbH, Liestal, Switzerland). Furthermore, visits to the brush and the concentrate feeder, and the milking order position were recorded. In comparison with nonlame cows, moderately lame cows had a longer lying duration, a longer average lying bout duration, and a greater lateral asymmetry in lying duration. Average locomotor activity, locomotor activity during 1 h after feed delivery or push-ups, and average neck activity were lower in moderately lame cows. Eating time and the number of eating chews (jaw movements) were reduced in moderately lame compared with nonlame cows, whereas no effect of moderate lameness was evident for ruminating time, number of ruminating chews and boluses, and average number of ruminating chews per bolus. Moderately lame cows visited the concentrate feeder and the brush less frequently, and they were further back in the milking order compared with nonlame cows. In conclusion, nonlame and moderately lame cows differed in a biologically relevant way in many of the behavioral variables investigated in this study. Therefore, the use of these behavioral changes seems to be promising to develop a tool for early lameness detection

Seven 3-methylidene-1H-indol-2(3H)-ones related to the multiple-receptor tyrosine kinase inhibitor sunitinib

The solid-state structures of a series of seven substituted 3-methylidene-1H-indol-2(3H)-one derivatives have been determined by single-crystal X-ray diffraction and are compared in detail. Six of the structures {(3Z)-3-(1H-pyrrol-2- ylmethylidene)-1H-indol-2(3H)-one, C13H10N2O, (2a); (3Z)-3-( 2-thienylmethylidene)-1H-indol-2(3H)-one, C13H9NOS, (2b); (3E)-3-(2-furylmethylidene)-1H-indol-2(3H)-one monohydrate, C13H9NO2 center dot H2O, (3a); 3-(1-methylethylidene)-1H-indol- 2(3H)-one, C11H11NO, (4a); 3-cyclohexylidene-1H-indol- 2(3H)-one, C14H15NO, (4c); and spiro[1,3-dioxane-2,3'-indolin]- 2'-one, C11H11NO3, (5)} display, as expected, intermolecular hydrogen bonding (N-H center dot center dot center dot O=C) between the 1H-indol-2(3H)-one units. However, methyl 3-(1-methylethylidene)- 2-oxo-2,3-dihydro-1H-indole-1-carboxylate, C13H13NO3, (4b), a carbamate analogue of (4a) lacking an N-H bond, displays no intermolecular hydrogen bonding. The structure of (4a) contains three molecules in the asymmetric unit, while (4b) and (4c) both contain two independent molecules

Redefining Palliative Care-A New Consensus-Based Definition.

The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. The main objective of this article is to present the research behind the new definition. The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span

A monolithic integrated photonic microwave filter

[EN] Meeting the increasing demand for capacity in wireless networks requires the harnessing of higher regions in the radiofrequency spectrum, reducing cell size, as well as more compact, agile and power-efficient base stations that are capable of smoothly interfacing the radio and fibre segments. Fully functional microwave photonic chips are promising candidates in attempts to meet these goals. In recent years, many integrated microwave photonic chips have been reported in different technologies. To the best of our knowledge, none has monolithically integrated all the main active and passive optoelectronic components. Here, we report the first demonstration of a tunable microwave photonics filter that is monolithically integrated into an indium phosphide chip. The reconfigurable radiofrequency photonic filter includes all the necessary elements (for example, lasers, modulators and photodetectors), and its response can be tuned by means of control electric currents. This is an important step in demonstrating the feasibility of integrated and programmable microwave photonic processors.The authors acknowledge financial support from the Spanish Centro para el Desarrollo Tecnologico Industrial (CDTI) through the NEOTEC start-up programme, the European Commission through the 7th Research Framework Programme project, Photonic Advanced Research and Development for Integrated Generic Manufacturing (FP7-PARADIGM), the Generalitat Valenciana through the Programa para grupos de Investigacion de Excelencia (PROMETEO) project code 2013/012, the Spanish Ministerio de Economia y Comercio (MINECO) via project TEC2013-42332-P, PIF4ESP, and the Unwersitat Politecnica de Valencia (UPVOV) through projects 10-3E-492 and 08-3E-008 funded by the Fondos Europeos de Desarrollo Regional (FEDER). J.S. Fandino acknowledges financial support from Formacion de Profesorado Universitario (FPU) grant AP2010-1595.Sanchez Fandiño, JA.; Muñoz Muñoz, P.; Doménech Gómez, JD.; Capmany Francoy, J. (2017). A monolithic integrated photonic microwave filter. Nature Photonics. 11(2):124-129. https://doi.org/10.1038/NPHOTON.2016.233S124129112Novak, D. et al. Radio-over-fiber technologies for emerging wireless systems. IEEE J. Quantum Electron. 52, 1–11 (2016).Waterhouse, R. & Novak, D. Realizing 5G: microwave photonics for 5G mobile wireless systems. IEEE Microw. Mag. 16, 84–92 (2015).Won, R. Microwave photonics shines. Nat. Photon. 5, 736 (2011).Capmany, J. & Novak, D. Microwave photonics combines two worlds. Nat. Photon. 1, 319–330 (2007).Yao, J. Microwave photonics. J. Lightw. Technol. 27, 314–335 (2009).Andrews, J. G. et al. What will 5G be? IEEE J. Sel. Areas Commun. 32, 1065–1082 (2014).Gosh, A., et al. 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Integrated InP–InGaAsP tuneable coupled ring optical bandpass filters with zero insertion loss. Opt. Express 19, 7816–7826 (2011).Fandiño, J. S. & Muñoz, P. Photonics-based microwave frequency measurement using a double-sideband suppressed-carrier modulation and an InP integrated ring-assisted Mach–Zehnder interferometer filter. Opt. Lett. 38, 4316–4319 (2013).Burla, M. et al. On-chip ultra-wideband microwave photonic phase shifter and true time delay line based on a single phase-shifted waveguide Bragg grating. In IEEE International Topical Meeting on Microwave Photonics 92–95 (IEEE, 2013).Shi, W., Veerasubramanian, V., Patel, D. & Plant, D. Tuneable nanophotonic delay lines using linearly chirped contradirectioinal couplers with uniform Bragg gratings. Opt. Lett. 39, 701–703 (2014).Guan, B. et al. CMOS compatible reconfigurable silicon photonic lattice filters using cascaded unit cells for RF-photonic processing. IEEE J. Sel. Top. Quantum Electron. 20, 359–368 (2014).Khan, M. H. et al. Ultrabroad-bandwidth arbitrary radiofrequency waveform generation with a silicon photonic chip-based spectral shaper. Nat. Photon. 4, 117–122 (2010).Pagani, M. et al. Instantaneous frequency measurement system using four-wave mixing in an ultra-compact long silicon waveguide. In Proc. 41st European Conf. on Optical Communication (ECOC) 1–3 (IEEE, 2015).Khilo, A. et al. Photonic ADC: overcoming the bottleneck of electronic jitter. Opt. Express 20, 4454–4469 (2012).Wang, J. et al. Reconfigurable radio-frequency arbitrary waveforms synthesized in a silicon photonic chip. Nat. Commun. 6, 5957 (2015).Marpaung, D. et al. Si3N4 ring resonator-based microwave photonic notch filter with an ultrahigh peak rejection. Opt. Express 21, 23286–23294 (2013).Zhuang, L. et al. Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links. Opt. Express 21, 25999–26013 (2013).Marpaung, D., Chevalier, L., Burla, M. & Roeloffzen, C. Impulse radio ultrawideband pulse shaper based on a programmable photonic chip frequency discriminator. Opt. Express 19, 24838–24848 (2011).Marpaung, D. On-chip photonic-assisted instantaneous microwave frequency measurement system. IEEE Photon. Technol. Lett. 25, 837–840 (2013).Burla, M. et al. On-chip CMOS compatible reconfigurable optical delay line with separate carrier tuning for microwave photonic signal processing. Opt. Express 19, 21475–21484 (2011).Tan, K. et al. Photonic-chip-based all-optical ultra-wideband pulse generation via XPM and birefringence in a chalcogenide waveguide. Opt. Express 21, 2003–2011 (2013).Pagani, M. et al. Tuneable wideband microwave photonic phase shifter using on-chip stimulated Brillouin scattering. Opt. Express 22, 28810–28818 (2014).Pérez, D., Gasulla, I. & Capmany, J. Software-defined reconfigurable microwave photonics processor. Opt. Express 23, 14640–14654 (2015).Capmany, J., Gasulla, I. & Pérez, D. 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Solid-phase molecular recognition of cytosine based on proton-transfer reaction. Part II. supramolecular architecture in the cocrystals of cytosine and its 5-Fluoroderivative with 5-Nitrouracil

<p>Abstract</p> <p>Background</p> <p>Cytosine is a biologically important compound owing to its natural occurrence as a component of nucleic acids. Cytosine plays a crucial role in DNA/RNA base pairing, through several hydrogen-bonding patterns, and controls the essential features of life as it is involved in genetic codon of 17 amino acids. The molecular recognition among cytosines, and the molecular heterosynthons of molecular salts fabricated through proton-transfer reactions, might be used to investigate the theoretical sites of cytosine-specific DNA-binding proteins and the design for molecular imprint.</p> <p>Results</p> <p>Reaction of cytosine (Cyt) and 5-fluorocytosine (5Fcyt) with 5-nitrouracil (Nit) in aqueous solution yielded two new products, which have been characterized by single-crystal X-ray diffraction. The products include a dihydrated molecular salt (CytNit) having both ionic and neutral hydrogen-bonded species, and a dihydrated cocrystal of neutral species (5FcytNit). In CytNit a protonated and an unprotonated cytosine form a triply hydrogen-bonded aggregate in a self-recognition ion-pair complex, and this dimer is then hydrogen bonded to one neutral and one anionic 5-nitrouracil molecule. In 5FcytNit the two neutral nucleobase derivatives are hydrogen bonded in pairs. In both structures conventional N-H^...O, O-H^...O, N-H^+...N and N-H^...N^-intermolecular interactions are most significant in the structural assembly.</p> <p>Conclusion</p> <p>The supramolecular structure of the molecular adducts formed by cytosine and 5-fluorocytosine with 5-nitrouracil, CytNit and 5FcytNit, respectively, have been investigated in detail. CytNit and 5FcytNit exhibit widely differing hydrogen-bonding patterns, though both possess layered structures. The crystal structures of CytNit (D<it>p</it>k_a= -0.7, molecular salt) and 5FcytNit (D<it>p</it>k_a= -2.0, cocrystal) confirm that, at the present level of knowledge about the nature of proton-transfer process, there is not a strict correlation between the D<it>p</it>k_avalues and the proton transfer, in that the acid/base <it>p</it>k_astrength is not a definite guide to predict the location of H atoms in the solid state. Eventually, the absence in 5FcytNit of hydrogen bonds involving fluorine is in agreement with findings that covalently bound fluorine hardly ever acts as acceptor for available Brønsted acidic sites in the presence of competing heteroatom acceptors.</p

Transport of Anthocyanins and other Flavonoids by the Arabidopsis ATP-Binding Cassette Transporter AtABCC2

Flavonoids have important developmental, physiological, and ecological roles in plants and are primarily stored in the large central vacuole. Here we show that both an ATP-binding cassette (ABC) transporter(s) and an H+-antiporter(s) are involved in the uptake of cyanidin 3-O-glucoside (C3G) by Arabidopsis vacuolar membrane-enriched vesicles. We also demonstrate that vesicles isolated from yeast expressing the ABC protein AtABCC2 are capable of MgATP-dependent uptake of C3G and other anthocyanins. The uptake of C3G by AtABCC2 depended on the co-transport of glutathione (GSH). C3G was not altered during transport and a GSH conjugate was not formed. Vesicles from yeast expressing AtABCC2 also transported flavone and flavonol glucosides. We performed ligand docking studies to a homology model of AtABCC2 and probed the putative binding sites of C3G and GSH through site-directed mutagenesis and functional studies. These studies identified residues important for substrate recognition and transport activity in AtABCC2, and suggest that C3G and GSH bind closely, mutually enhancing each other’s binding. In conclusion, we suggest that AtABCC2 along with possibly other ABCC proteins are involved in the vacuolar transport of anthocyanins and other flavonoids in the vegetative tissue of Arabidopsis

Redefining palliative care-a new consensus-based definition

Context: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. Objective: The main objective of this article is to present the research behind the new definition. Methods: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. Results: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. Conclusion: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span