36 research outputs found

    Mitochondria: It is all about energy

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    Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolutionbased intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.Clinical Psychoneuroimmunology (the University of Granada and PNI Europe

    Mitochondria: It is all about energy

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    Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases

    Surgical treatment of anorectal melanoma:a systematic review and meta-analysis

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    BACKGROUND: Anorectal melanoma is a rare neoplasm with a poor prognosis. The surgical approaches for anorectal melanoma can be categorized into local excision (procedures without lymph node removal and preservation of the rectum) and extensive resection (procedures with rectum and pararectal lymph node removal). The aim of this systematic review and meta-analysis was to compare the survival of patients who underwent extensive resection with that of patients who underwent local excision, stratifying patients according to tumour stage. METHODS: A literature review was performed according to PRISMA guidelines by searching MEDLINE/PubMed for manuscripts published until March 2021. Studies comparing survival outcomes in patients with anorectal melanoma who underwent local excision versus extensive resection were screened for eligibility. Meta-analysis was performed for overall survival after the different surgical approaches, stratified by tumour stage. RESULTS: There were 347 studiesidentified of which 34 were included for meta-analysis with a total of 1858 patients. There was no significant difference in overall survival between the surgical approaches in patients per stage (stage I odds ratio 1.30 (95 per cent c.i. 0.62 to 2.72, P = 0.49); stage II odds ratio 1.61 (95 per cent c.i. 0.62 to 4.18, P = 0.33); stage I–III odds ratio 1.19 (95 per cent c.i. 0.83 to 1.70, P = 0.35). Subgroup analyses were conducted for the time intervals (<2000, 2001–2010 and 2011–2021) and for continent of study origin. Subgroup analysis for time interval and continent of origin also showed no statistically significant differences in overall survival. CONCLUSION: No significant survival benefit exists for patients with anorectal melanoma treated with local excision or extensive resection, independent of tumour stage

    The HST Key Project on the Extragalactic Distance Scale XVII. The Cepheid Distance to NGC 4725

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    The distance to NGC 4725 has been derived from Cepheid variables, as part of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale. Thirteen F555W (V) and four F814W (I) epochs of cosmic-ray-split Wide Field and Planetary Camera 2 observations were obtained. Twenty Cepheids were discovered, with periods ranging from 12 to 49 days. Adopting a Large Magellanic Cloud distance modulus and extinction of 18.50+/-0.10 mag and E(V-I)=0.13 mag, respectively, a true reddening-corrected distance modulus (based on an analysis employing the ALLFRAME software package) of 30.50 +/- 0.16 (random) +/- 0.17 (systematic) mag was determined for NGC 4725. The corresponding of distance of 12.6 +/- 1.0 (random) +/- 1.0 (systematic) Mpc is in excellent agreement with that found with an independent analysis based upon the DoPHOT photometry package. With a foreground reddening of only E(V-I)=0.02, the inferred intrinsic reddening of this field in NGC 4725, E(V-I)=0.19, makes it one of the most highly-reddened, encountered by the HST Key Project, to date.Comment: To be published in The Astrophysical Journal, Vol. 512 (1999). 34 pages, LaTeX, 9 jpg figure

    'We don't know for sure':discussion of uncertainty concerning multigene panel testing during initial cancer genetic consultations

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    Pre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors' communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations of counselors discussing a multigene panel with a simulated patient were videotaped. Simulated patients represented a counselee who had had multiple cancer types, according to a script. Before and afterwards, counselors completed a survey. Counselors' uncertainty expressions, initiating and the framing of expressions, and their verbal responses to scripted uncertainties of the simulated patient were coded by two researchers independently. Coding was done according to a pre-developed coding scheme using The Observer XT software for observational analysis. Additionally, the degree of SDM was assessed by two observers. Correlation and regression analyses were performed to assess associations of communicated uncertainties, responses and the extent of SDM, with counselors' background characteristics. In total, twenty-nine counselors, including clinical geneticists, genetic counselors, physician assistants-in-training, residents and interns, participated of whom working experience varied between 0 and 25 years. Counselors expressed uncertainties mainly regarding scientific topics (94%) and on their own initiative (95%). Most expressions were framed directly (77%), e.g. We don't know, and were emotionally neutral (59%; without a positive/negative value). Counselors mainly responded to uncertainties of the simulated patient by explicitly referring to the uncertainty (69%), without providing space for further disclosure (66%). More experienced counselors provided less space to further disclose uncertainty (p <0.02), and clinical geneticists scored lower on SDM compared with other types of counselors (p <0.03). Our findings that counselors mainly communicate scientific uncertainties and use space-reducing responses imply that the way counselors address counselees' personal uncertainties and concerns during initial cancer genetic counseling is suboptimal

    ‘We don’t know for sure’: discussion of uncertainty concerning multigene panel testing during initial cancer genetic consultations

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    Pre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors’ communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations of counselors discussing a multigene panel with a simulated patient were videotaped. Simulated patients represented a counselee who had had multiple cancer types, according to a script. Before and afterwards, counselors completed a survey. Counselors’ uncertainty expressions, initiating and the framing of expressions, and their verbal responses to scripted uncertainties of the simulated patient were coded by two researchers independently. Coding was done according to a pre-developed coding scheme using The Observer XT software for observational analysis. Additionally, the degree of SDM was assessed by two observers. Correlation and regression analyses were performed to assess associations of communicated uncertainties, responses and the extent of SDM, with counselors’ background characteristics. In total, twenty-nine counselors, including clinical geneticists, genetic counselors, physician assistants-in-training, residents and interns, participated of whom working experience varied between 0 and 25 years. Counselors expressed uncertainties mainly regarding scientific topics (94%) and on their own initiative (95%). Most expressions were framed directly (77%), e.g. We don’t know, and were emotionally neutral (59%; without a positive/negative value). Counselors mainly responded to uncertainties of the simulated patient by explicitly referring to the uncertainty (69%), without providing space for further disclosure (66%). More experienced counselors provided less space to further disclose uncertainty (p < 0.02), and clinical geneticists scored lower on SDM compared with o

    Water en olie, dat mengt niet vanzelf.: Onderzoek naar theoriegebruik bij lijfstijlprogramma's.

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    Gezondheidsproblemen, zoals overgewicht, roken en diabetes komen veelvuldig voor in de Nederlandse samenleving. Om het aantal gezondheidsproblemen terug te dringen is er in de afgelopen jaren gekozen voor een leefstijlbenadering. In een leefstijlbenadering staat niet één punt centraal dat moet veranderen aan het ongewenste gedrag (bijvoorbeeld stoppen met roken), maar een complex van gedragingen en gewoonten. Wanneer er veranderingen optreden zijn deze een krachtigere voorspeller van uiteindelijke gezondheidseffecten, dan veranderingen die het gevolg zijn van een enkelvoudige benadering. Het bewerkstelligen van deze veranderingen lijkt echter moeilijker. Het Ministerie van Volksgezondheid, Welzijn en Sport (VWS) zet daarom verschillende maatregelen in om de leefstijl van de Nederlandse bevolking te veranderen. Eén van de middelen is het subsidiëren van campagnes waarin de (ongezonde) leefstijl centraal staat. Deze 'leefstijlcampagnes' hebben tot doel om de Nederlandse bevolking bewust te maken van de gezondheidsnorm en het aanzetten tot een gezonder leefpatroon. Of deze campagnes effect sorteren in de samenleving wordt in grote mate bepaald door de keuzes die gemaakt zijn tijdens de ontwikkeling ervan. Hierbij gaat het dan niet zozeer om waar het campagneteam voor kiest, maar het waarom van de keuze. Keuzes dienen idealiter niet alleen gebaseerd te worden op (praktijk)ervaring en intuïtie, maar ook op wetenschappelijke theorieën. Het gebruik van theorieën wordt in de praktijk echter vaak als iets lastigs ervaren, zoals een respondent in dit onderzoek het verwoordde: 'Je hebt een soort water en olie naast elkaar, dat mengt niet vanzelf'
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