25 research outputs found

    The Transcription Factor Twist1 Has a Significant Role in Mycosis Fungoides (MF) Cell Biology: An RNA Sequencing Study of 40 MF Cases

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    The purpose of this RNA sequencing study was to investigate the biological mechanism underlying how the transcription factors (TFs) Twist1 and Zeb1 influence the prognosis of mycosis fungoides (MF). We used laser-captured microdissection to dissect malignant T-cells obtained from 40 skin biopsies from 40 MF patients with stage I–IV disease. Immunohistochemistry (IHC) was used to determinate the protein expression levels of Twist1 and Zeb1. Based on RNA sequencing, principal component analysis (PCA), differential expression (DE) analysis, ingenuity pathway analysis (IPA), and hub gene analysis were performed between the high and low Twist1 IHC expression cases. The DNA from 28 samples was used to analyze the TWIST1 promoter methylation level. In the PCA, Twist1 IHC expression seemed to classify cases into different groups. The DE analysis yielded 321 significant genes. In the IPA, 228 significant upstream regulators and 177 significant master regulators/causal networks were identified. In the hub gene analysis, 28 hub genes were found. The methylation level of TWIST1 promoter regions did not correlate with Twist1 protein expression. Zeb1 protein expression did not show any major correlation with global RNA expression in the PCA. Many of the observed genes and pathways associated with high Twist1 expression are known to be involved in immunoregulation, lymphocyte differentiation, and aggressive tumor biology. In conclusion, Twist1 might be an important regulator in the disease progression of MF

    Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

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    Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

    Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

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    There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Positron annihilation studies on vacancy defects in group IV semiconductors

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    Electrical properties of semiconductor materials are greatly influenced by point defects such as vacancies and interstitials. These defects are common and form during the growth and processing of the material. Positron annihilation spectroscopy is a method suitable for detecting and studying vacancy-type lattice defects. In this work, the formation, properties, and annealing of vacancy defects is studied in silicon, silicon-germanium, and germanium. Defects consisting of a vacancy and one or several donor atoms are one of the most common defects causing electron trapping and deactivation of n-type doping in silicon and silicon-germanium. In this work, the studies in silicon-germanium show that several germanium atoms accumulate around the vacancy-phosphorus (V-P) pair during the annealing of the samples. The increased Ge-decoration pulls the energy level (-/- -) down into the band-gap and makes the V-P pair decorated by several Ge atoms an especially effective trap for conduction electrons. The positron trapping in a vacancy surrounded by three As atoms (V-As3) is studied in highly As-doped Si. The positron detrapping from the V-As3 defect at high temperatures is observed and a binding energy of 0.27(3) eV of a positron to the V-As3 complex is determined. Defects can also be introduced deliberately by neutron-irradiation and ion-implantation. These techniques offer possibilities for studying the generation and annealing of vacancy defects. In this work, neutron-irradiated germanium is studied. Irradiation induced divacancy defects that are stable at room temperature are observed. A negative charge state of a divacancy is found to stabilize the defect even at 400°C. The divacancy is shown to form bigger clusters before the final recovery at 500°C. Finally, B-doping related problems are studied. The results show that He-implantation produces nanovoids that trap interstitials formed during the B-implantation, reducing the implantation related damage. The positron studies on the excimer laser annealed Si support theoretical calculations, which suggest vacancy formation at the maximum melt depth

    Luontokokemuksia sijaishuollon kokonaisvaltaisen kuntoutuksen tueksi

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    Työn tilaajana on Sauma Kodit Ankkuri, joka keskittyy moniammatillisesti toteutettaviin erityistason lastensuojelu palveluihin. OpinnĂ€ytetyö vastaa esiin nousseeseen tarpeeseen kehittÀÀ opas luontotoiminnan vakiinnuttamiseen kuntoutuksen tueksi. OpinnĂ€ytetyön teoreettinen viitekehys rakentuu luonnon hyvinvointivaikutuksista huomioiden yksikön psykiatrisen kuntoutuksen tarjoaman. OpinnĂ€ytetyössĂ€ hyödynnettiin ohjaajille suunnattua kyselyĂ€ ja asiantuntija haastattelua. Kyselyn avulla kartoitettiin, kuinka luontoelĂ€mykset on otettu yksiköissĂ€ kĂ€yttöön, millaista kokemusta ja osaamista ohjaajilta löytyy sekĂ€ motivaatiota tarjota luontokokemuksia nuorille. Haastattelun tarkoituksena oli saada kĂ€ytĂ€nnöntietoa, miten luontokokemuksia luodaan. Tutkimus tuotti tietoa siitĂ€, mitĂ€ luontotoiminta on, missĂ€ se tapahtuu ja millaisia vaikutuksia sillĂ€ on. OpinnĂ€ytteen tuotoksena syntyi opas, joka keskittyy ratkaisemaan kyselyssĂ€ ilmenneitĂ€ haasteita luontotoiminnalle, joita olivat mielialan vaihtelut, tiedon puute ja resurssit. Luontotoiminnan hyödyt terveydelle nĂ€hdÀÀn kiistattomina, joten se voitaisiin nĂ€hdĂ€ tĂ€ydentĂ€vĂ€nĂ€ ”peruspakettina” lÀÀkehoidon ja terapeuttisten keskustelujen yhteydessĂ€. OpinnĂ€ytetyön tuloksena on opas ”Luontokokemuksia sijaishuollon kokonaisvaltaisen kuntoutuksen tueksi”. Opas rakennettiin vastaamaan kysymykseen, miten sijaishuollossa voidaan luoda luontokokemuksia kuntoutuksen tueksi. Oppaan keskeisin sisĂ€ltö keskittyy luontoon tutustumiseen ja spontaaniuteen, jolloin se ei vaadi erillisiĂ€ vĂ€lineitĂ€ ja on mahdollista varallisuudesta riippumatta. Vuosikellon muotoon koottu luontokokemuksien opas on suunnattu opinnĂ€ytteen tilaajalle lastensuojelun kĂ€yttöön. Opas toimii tukena erilaisissa palveluissa, kuten nuorisotyössĂ€ toimiville ammattilaisille ja vapaaehtoisille luontolĂ€htöisen toiminnan toteuttamisen tueksi. Kaikki luontotoiminnat voidaan yhdistÀÀ sosiaalisten taitojen harjoitteluun, perheterapiaan tai pelkĂ€stÀÀn tiedon jakamiseen

    Eettisen johtamisen toteutuminen ja sen yhteys työhyvinvointiin sosiaali- ja terveysalan työntekijöiden arvioimana

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    This master’s degree thesis was made in Diaconia University of Applied Sciences as a part of SotePeda 24/7 -project. One of the main goals of this project was to improve and develop knowledge of leadership and ethical knowledge and how these are being taught in social and healthcare. There were 22 universities of applied sciences and 2 universities involved in the project. This thesis is a quantitative research and analysed by statistically descriptive analysis.    The aim of this thesis was to find out how social and health care workers evaluate realisation of ethical leadership and well-being at work and how ethical leadership impacts well-being at work. We had seven trade unions as cooperation partners. The research was made using a Webropol survey and there were 1171 respondents. Respond percentage was 7.7 %. Of those respondents 53 % had a degree in healthcare and 37 % in social services, while the rest had some other degree.   The main result of this thesis was that there is a strong correlation between ethical leadership and well-being at work. If leadership was not ethical, the employee’s well-being was compromised. Leadership in social and healthcare is in a key role and affects the personnel’s well-being and willingness to change workplace. Education and development of leadership in social and healthcare is important in the future. It is important as well to pay attention and strengthen the knowledge of ethical leadership.TĂ€mĂ€ ylemmĂ€n ammattikorkeakoulututkinnon opinnĂ€ytetyö kĂ€sittelee sosiaali- ja terveysalan työntekijöiden arvioita eettisen johtamisen toteutumisesta ja sen yhteydestĂ€ työhyvinvointiin. OpinnĂ€ytetyö on toteutettu Diakonia-ammattikorkeakoulussa osana 24 suomalaisen korkeakoulun yhteistĂ€ SotePeda 24/7 -hanketta. Hankkeen yhtenĂ€ tarkoituksena on lisĂ€tĂ€ johtamisosaamista sekĂ€ kehittÀÀ sosiaali- ja terveysalan koulutusuudistuksen yhteydessĂ€ eettistĂ€ osaamista ja kouluttamista siihen. OpinnĂ€ytetyö on tehty yhteistyössĂ€ seitsemĂ€n sosiaali- ja terveysalan ammattijĂ€rjestön kanssa heidĂ€n jĂ€senistölleen kyselytutkimuksena. Webropol-kyselyyn vastasi kaikkiaan 1 171 sosiaali- ja terveysalan ammattiliiton jĂ€sentĂ€. Vastausprosentti oli 7,7. Vastaajista 53 %:lla oli terveysalan ja 37 %:lla sosiaalialan tutkinto. Lopuilla kymmenellĂ€ prosentilla vastaajista oli jokin muu tutkinto. OpinnĂ€ytetyössĂ€ selvitettiin sosiaali- ja terveysalan henkilöstön arvioita siitĂ€, miten eettinen johtaminen toteutuu työpaikoilla ja miten työntekijĂ€t arvioivat eettisen johtamisen olevan yhteydessĂ€ työhyvinvointiin. Kyselyaineiston kvantitatiivisen analyysin lisĂ€ksi opinnĂ€ytetyötutkimusta varten toteutettiin tietokantahakuja eettisestĂ€ johtamisesta ja työhyvinvoinnista. Tuloksena voidaan todeta eettisen johtamisen korreloivan vahvasti työhyvinvoinnin kanssa. MitĂ€ huonommaksi eettisen johtamisen toteutuminen arvioitiin, sitĂ€ huonommaksi arvioitiin työhyvinvointi. Sosiaali- ja terveysalan johtaminen on tĂ€rkeĂ€ssĂ€ asemassa henkilökunnan jaksamisessa ja työssĂ€ pysymisessĂ€. Sote-alan johtamiskoulutukseen ja eettisen johtamisen vahvistamiseen tulisi tulevaisuudessa kiinnittÀÀ huomiota ja kehittÀÀ sitĂ€

    Sex-related effects in the superhydrophobic properties of damselfly wings in young and old Calopteryx splendens.

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    Numerous sex-related morphological adaptations are connected to reproductive behavior in animals. For example, females of some insect species can submerge during oviposition, which may lead to sex-related adaptations in the hydrophobicity (water-repellency) due to specialization of certain morphological structures. On the other hand, ageing can cause changes in hydrophobicity of the surface, because the morphological structures can wear with age. Here, we investigated sex-and age-related differences in wing hydrophobicity and in morphology (spine density, wax cover characteristics, size of females' pseudopterostigma) potentially related to hydrophobicity of Calopteryx splendens damselflies. Hydrophobicity was measured with two methods, by measuring the contact angle (CA) between a wing and water droplet, and by dipping a wing into water and measuring forces needed to submerge, withdraw, and pull-out a wing from water. We found that C. splendens wings are superhydrophobic, having mean CAs of 161°. The only sex and age related difference in the hydrophobicity measurements was that young females had stronger amplitude of force fluctuations during withdrawal of wings from water than young males. This suggests that young females may form less uniform air pockets on their wings while submerged. From the morphological structures measured here, the only sex related finding was that old females had denser spine cover than young females in their wing veins. The difference may be explained by better survival of females with denser spine cover. The most important morphological character that predicted superhydrophobicity was the prevalence of long wax rods on wing veins. In addition, female pseudopterostigma area (a trait present only in females) was negatively related to pull-out force, suggesting that large pseudopterostigmas might help females to emerge from water following oviposition. The subtle sex-related differences in hydrophobicity could be explained by the fact that both sexes must resist rain, and males are occasionally in contact with water
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