Orto-fluoronoidun ja -aminoidun atsobentseenin synteesi ja spektroskooppinen karakterisointi

Atsobentseeni on valo-aktiivinen molekyyli, jonka trans-isomeeri muuttuu cis-isomeeriksi UV- tai näkyvällä valolla säteilyttäessä. Cis-isomeerin termisen relaksaation nopeutta trans-isomeeriksi sanotaan molekyylin elinajaksi. Molekyylin absorptioalueeseen ja elinaikaan voidaan vaikuttaa siihen liitettävillä substituenteilla. Tehty työ pohjautuu Ahmed et. al. artikkeliin, jossa yhdistettiin orto-fluorinointi ja -aminointi atsobentseenimolekyylien ominaisuuksien kontrollointiin. Orto-asemaan liitetty fluoriatomi lisää molekyylin elinaikaa, ja amiiniryhmä vahvistaa ja siirtää n → π^* transition absorptiopiikkiä näkyvän valon alueelle. Työssä syntetisoitiin 5 molekyyliä, 4 fluori- ja/tai piperidiini substituoitua molekyyliä sekä bromi- ja piperidiini substituoitu molekyyli. Molekyyleille määritettiin absorptiospektrit sekä elinajat. Molekyylien n → π^* transition absorptio piperidiinin tapauksessa on näkyvällä aallonpituusalueella, mutta lyhemmillä aallonpituuksilla kuin aiemman artikkelin vastaavat rakenteet pyrrolidiini amiinilla. Piperidiini aiemman pyrrolidiinin sijasta pidensi elinaikaa kolmen molekyylin tapauksessa n. 60 kertaiseksi, ja pisimmän elinajan omaavan molekyylin tapauksessa kuusinkertaiseksi. Elinajat olivat molekyylille 1 445h, 2 10min, 3 300min, 4 59min

The long-term outcome of Kienböck's disease

Numerous surgical methods have been used in the treatment of Kienböck’s disease, methods based on either modification of the lunar load, improvement of the blood flow of the lunate, or are based on removal of the damaged lunate and its replacement by various materials. Recent steps have been total wrist arthrodesis and proximal row carpectomy. The etiology of the disease is still unclear, with little research available on the natural course. No reliable comparison has been presented of the different treatment methods, and treatment options are based on the re-sults with various therapies at different stages of the disease. The purpose of our study was to discover the results in long-term follow-up from three different surgical procedures and prognosis for untreated patients. Surgical treatments included silicone implant arthroplasty, SLA (53 patients), radial shortening osteotomy, RSO (16 patients), and titanium implant arthroplasty (11 patients); the untreated group comprised 8 patients. The studies were retrospective and non-randomized. RSO was done for ulna minus variance patients. The degree of disease was in all groups mainly Lichtman -Degnan stages IIIA-IIIB. The follow-up times were 27 years for silicone patients, 25 years for osteotomies, 11 years for titanium implants, and 18 years for untreated patients ( mean 27 years from onset of symptoms). In SLA the result was impaired by silicone-induced synovitis and bone cyst formation in 78% of patients. Revisions were maid for 22%. In osteotomies, the progression of the disease led to two revisions (12%) and four osteotomies (25%) had poor results. With a titanium implant, poor results were associated with two implant dislocations. Silicone-implant patients and untreated patients had the highest incidence of pain at rest and during exertion ( VAS during exertion 5.2 in both). Full pain-relief ranged from 0% (untreated) to -21% (osteotomy). Range on motion (ROM) and grip strength imp-roved in all groups but remained generally significantly worse than on the healthy side. In the osteotomy group, ROM (88%) and grip strength (95%) were the best. Radiological changes progressed in each treatment group. In silicone-patients, arthrosis existed in 91%, and our arthrosis index was the highest, 7.7/15. Wrist collapse increased as well. In osteotomies, arthrosis existed in 71% and for titanium-implant patients in 45% with an index of 4.4 in both. With untreated, arthrosis was in 89% and an index 5.4. However, untreated disease did not lead to severe arthrotic changes. Functional ability remained good according to the DASH score: in osteotomies 6.1, with titanium implants 9.6, and for those untreated 11.3, while in silicone-implant patients it was 25.4. The corresponding result was in terms of working ability: in silicone-implant patients, 21% were incapacitated and for osteotomies this was 7%. Of the untreated patients, 25% had switched to lighter work, as had 9% of titanium-implant patients. The results according to Mayo wrist scoring were similar, with the best score for osteotomies, 79, and the worst for silicone-implant patients, 54.8. Osteotomy yielded a clear benefit for 75% of the patients in long-term follow-up, although the failure rate was high, 25%. The functional result of untreated patients was moderately good, although their wrist degenerative changes increased. The result from titanium implant was skewed by two dislocations, and the operative technique currently do not completely eliminate this problem. Moreover, treatment indications require further attention. In future, prospective studies would be needed to better assess the role and importance of surgical treatments. Similarly, the natural course of the disease should also become better known, so that the actual effect of these treatment methods on the course of the disease would become clear.Kienböckin taudin hoidosta on julkaistu vähän pitkäaikaistuloksia, eikä taudin luonnollisesta kulusta ole riittävästi tietoa. Taudin etiologia on edelleen epäselvä. Selvitimme hoitamattomien sekä kolmella leikkaushoidolla, silikoni-implanttiartroplastialla (SLA), radiuksen lyhennysosteotomialla (RSO) sekä titaani-implanttiartroplastialla (TLA) hoidettujen pitkän seuranta-ajan tuloksia. Radiuksen lyhennysosteotomiat tehtiin ulnan minus varianssissa. Tutkimukset olivat retrospektiivisiä.Hoitamattomia oli 8 , SLA-aineistossa 53 , RSO:ssa 14 ja TLA:ssa 11 potilasta. TLA potilaat oli hoidettu TAYS:ssa, muut Sairaala Ortonissa. Hoitotiedot ja alkuvaiheen röntgenkuvat saatiin sairaaloiden tiedostoista. Keskimääräinen seuranta-aika oli hoitamattomilla 18, SLA:ssa 27, RSO:ssa 25 ja TLA:ssa 11 vuotta.Taudin aste oli valtaosalla Lichtman-Degnan IIIA-IIIB kaikissa ryhmissä . Seurantatutkimuksessa potilaat arvioivat kivun VAS-asteikolla (0-10) ja toiminnallisen tuloksen DASH-pisteytyksellä. Lisäksi he kirjasivat oireet, mahdolliset myöhemmät hoitotoimenpiteet, ja työkykyyn liittyvät asiat. Paikallislöydökset kirjattiin, mitattiin ranteiden aktiiviset liikeradat ja puristusvoimat ja molemmat ranteet röntgenkuvattiin. Lunatummalasian astetta arvioitiin Lichtmanin ja Degnanin luokituksella. Ranteen korkeuden muutosta ,ulnaarisuuntaista siirtymää, luiden kulmamuutosta ja lunatumin muutosta arvioitiin, samoin ranteen artroosin esiintymistä ja vaikeusastetta.Tuloksia arvioitiin Mayo wrist scoringilla (MWS). SLA-ryhmässä tulosta huononi silikonisynoviitti ja ranneluiden kystamuutokset, joita todettiin 78%:lla. Revisioita tehtiin 22%:lle.Osteotomioissa sairauden progressio johti kahteen revisioon ja neljällä potilaalla (25%) tulos oli huono. Titaani-implantilla kaksi dislokaatiota johti huonoon tulokseen. Hoitamattomien ryhmässä ei ollut täysin kivuttomia, SLA:ssa kivuttomia oli 11%, RSO:ssa 21% ja TLA:ssa 18%. VAS (0-10) oli vastaavasti levossa keskimäärin 3.1, 2.2, 0.9 ja 0.5. Voimakkaassa rasituksessa VAS oli vastaavasti 5.2, 5.2, 3.0 ja 2.7. DASH pisteet olivat hoitamattomilla 11.3, RSO:ssa 6.1 ja TLA:ssa 9.6, joten toiminnallinen tila oli näillä hyvä. SLA:ssa pisteet olivat selvästi huonommat, keskimäärin 25.4 ja potilaista 21% jäi työkyvyttömiksi, RSO:ssa vastaavasti 7%.Hoitamattomissa 25% oli siirtynyt kevyempään työhön ja TLA:ssa 9%. Mayo wrist scoring oli paras RSO:ssa, keskimäärin 79 ja huonoin SLA:ssa, 54.8. Hoitamattomilla tulos oli kohtalaisen hyvä, vaikka ranteen degeneraatio lisääntyi. Lyhennysosteotomian tulos oli kivun ja toimintakyvyn suhteen 75%:lla hyvä korkeasta komplikaatiomäärästä huolimatta. SLA:ssa komplikaatiot johtivat huonoon lopputulokseen, eikä silikoni-implanttia suositella enää käytettäväksi Kienböckin taudissa. TLA:n tulosta huononsi implantin instabiliteettiin liittyneet kaksi implantin dislokaatiota, joten sen käyttöä ei varauksetta voida suositella. Jatkossa tarvitaan prospektiivisia vertailevia tutkimuksia kirurgisten hoitojen hyödyn selvittämiseksi. Samoin taudin luonnollista kulkua pitäisi tuntea paremmin, jolloin hoitotoimenpiteiden vaikutukset ja merkitys selventyisivät

Antinociception by Spinal and Systemic Oxycodone: Why Does the Route Make a Difference?

Background The pharmacology of oxycodone is poorly understood despite its growing clinical use. The discrepancy between its good clinical effectiveness after systemic administration and the loss of potency after spinal administration led the authors to study the pharmacodynamic effects of oxycodone and its metabolites using in vivo and in vitro models in rats. Methods Male Sprague-Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study the antinociceptive properties of morphine, oxycodone, and its metabolites oxymorphone and noroxycodone. Mu-opioid receptor agonist-stimulated GTPgamma[S] autoradiography was used to study G-protein activation induced by morphine, oxycodone, and oxymorphone in the rat brain and spinal cord. Spontaneous locomotor activity was measured to assess possible sedation or motor dysfunction. Naloxone and the selective kappa-opioid receptor antagonist nor-binaltorphimine were used to study the opioid receptor selectivity of the drugs. Results Oxycodone showed lower efficacy and potency to stimulate GTPgamma[S] binding in the spinal cord and periaqueductal gray compared with morphine and oxymorphone. This could relate to the fact that oxycodone produced only weak naloxone-reversible antinociception after intrathecal administration. It also suggests that the metabolites may have a role in oxycodone-induced analgesia in rats. Intrathecal oxymorphone produced strong long-lasting antinociception, whereas noroxycodone produced antinociception with very high doses only. Subcutaneous administration of oxycodone and oxymorphone produced thermal and mechanical antinociception that was reversed by naloxone but not by nor-binaltorphimine. Oxymorphone was more potent than oxycodone, particularly in the hot-plate and paw-pressure tests. Conclusions The low intrathecal potency of oxycodone in rats seems be related to its low efficacy and potency to stimulate mu-opioid receptor activation in the spinal cord

Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients with Obesity Undergoing Bariatric Surgery : A Randomized Clinical Trial

Publisher Copyright: © 2022 Authors. All rights reserved.Importance: Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor. Objective: To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery. Design, Setting, and Participants: This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022. Interventions: FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) Main Outcomes and Measures: The main outcome was weight reduction measured as the percentage of total weight loss (TWL). Results: Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P <.001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P =.006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P <.001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P <.001) in the placebo group; however, no difference was observed between the groups. Conclusions and Relevance: FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity. Trial Registration: ClinicalTrials.gov Identifier: NCT03391817.Peer reviewe

Red-light photoswitching of indigos in polymer thin films

Through simple synthetic derivatisation, the parent indigo dye becomes a red-light E-Z photoswitch exhibiting negative photochromism and tuneable thermal isomerisation kinetics. These attributes make indigo derivatives extremely attractive for applications related to materials and living systems. However, there is a lack of knowledge in translating indigo photoswitching dynamics from solution to solid state - the environment crucial for most applications. Herein, we study the photoswitching performance of six structurally distinct indigo derivatives in five polymers of varying rigidity. Three key strategies are identified to enable efficient photoswitching under red (660 nm) light: (i) choosing a soft polymer matrix to minimise its resistance toward the isomerisation, (ii) creating free volume around the indigo molecules through synthetic modifications, and (iii) applying low dye loading (80% Z form in the photostationary state) is nearly identical to that in solution. These findings thus pave the way for designing new red-light photochromic materials based on indigos.publishedVersionPeer reviewe

Outcome and patients' satisfaction after functional treatment of acute lateral ankle injuries at emergency departments versus family doctor offices

<p>Abstract</p> <p>Background</p> <p>In some Western countries, more and more patients seek initial treatment even for minor injuries at emergency units of hospitals. The initial evaluation and treatment as well as aftercare of these patients require large amounts of personnel and logistical resources, which are limited and costly, especially if compared to treatment by a general practitioner. In this study, we investigated whether outsourcing from our level 1 trauma center to a general practitioner has an influence on patient satisfaction and compliance.</p> <p>Methods</p> <p>This prospective, randomized study, included n = 100 patients who suffered from a lateral ankle ligament injury grade I-II (16, 17). After radiological exclusion of osseous lesions, the patients received early functional treatment and were shown physical therapy exercises to be done at home, without immobilization or the use of stabilizing ortheses. The patients were randomly assigned into two groups of 50 patients each: Group A (ER): Follow-up and final examination in the hospital's emergency unit. Group B (GP): Follow-up by general practitioner, final examination at hospital's emergency unit. The patients were surveyed regarding their satisfaction with the treatment and outcome of the treatment.</p> <p>Results</p> <p>Female and male patients were equally represented in both groups. The age of the patients ranged from 16 – 64 years, with a mean age of 34 years (ER) and 35 years (GP). 98% (n = 98) of all patients were satisfied with their treatment, and 93% (n = 93) were satisfied with the outcome. For these parameters no significant difference between the two groups could be noted (p = 0.7406 and 0.7631 respectively). 39% of all patients acquired stabilizing ortheses like ankle braces (Aircast, Malleoloc etc.) on their own initiative. There was a not significant tendency for more self-acquired ortheses in the group treated by general practicioners (p = 0,2669).</p> <p>Conclusion</p> <p>Patients who first present at the ER with a lateral ankle ligament injury grade I-II can be referred to a general practitioner for follow-up treatment without affecting patient satisfaction regarding treatment and treatment outcome.</p

Synthesis and characterization of indigo photoswitches

Controlling the function and properties of materials, pharmaceuticals and catalysts after manufacturing is essential for contemporary chemists. Such control can be achieved via use of molecular switches, which change their chemical and/or physical properties in response to external stimuli. Light is a particularly attractive stimulus because of its high degree of controllability without physical contact, and clean nature. Therefore, organic light-responsive molecules – photoswitches – are studied for such purposes. The synthesis of new photoswitches with different photochemical properties is needed for various applications. In the molecular design of such photoswitches, compatibility with different matrices such as polymers or elastomers, is necessary to be taken into account. In this thesis, three different previously unreported indigo photoswitches were designed and synthesized and their photochemical properties characterized in different environments. Photoswitches with similar indigo-core had been previously syntheized and characterized in solution, so the focus was to enable implementation to liquid crystalline and polymer matrices and study the photochemical properties in these environments, with a particular aim of obtaining indigo photoswitching in the solid state. The photochemical properties of the indigo photoswitches were first studied in solution, after which they were incorporated as dopants in liquid crystals and in polymer films. Photoisomerization efficiency, molar absorption coefficient, thermal stability of the metastable Z-isomer and fatigue resistance were determined. All studied molecules showed similar properties to reference molecules in solution: reversible and efficient photoswitching with moderate thermal life-times and high fatigue resistance. Photoswitching was less efficient in liquid crystals than in solutions, probably due to shorter Z-lifetimes dominating the photostationary states. All compounds showed fatigue resistance of over 50 cycles in liquid crystals. In a polymer film the photoswitching efficiency was higher than in liquid crystals but lower than in solution. Thermal lifetimes were multiple times longer than in a solution, and all photoswitches could be switched to both direction with 660 nm and 525 nm light. Indigo photoswitches studied in this work were compatible with liquid crystals and polymer films. Photoswitching was observed in all studied environments with moderate E to Z conversion with low-energy irradiation. Regarding the synthetic routes, more studies for optimization of the reactions is required. The synthesized indigo photoswitches are ready for further studying as crosslinkers in liquid crystal elastomers or polymer network

Leopard 1 evakuointipanssarivaunun huolto-ohjelman kehittäminen

Tämä opinnäytetyö syntyi tekijän omaan työtehtävään liittyvästä tarpeesta perehtyä Leopard 1- alustaisen evakuointipanssarivaunun huolto-ohjelman sisältöön. Tutkimusongelmana oli se, miten olemassa olevan huoltodokumentaation mukaista huolto-ohjelmaa tulisi kehittää, jotta se ennalta ehkäisisi kansallisen käyttöprofiilin ja suomalaisten olosuhteiden aiheuttamien kuormitusten vaikutuksen vaunun käyttövarmuuteen. Jo tutkimuksen esityön aikana selvisi, että tavoitteena ei voi olla uusien, käyttövalmiiden huoltotaulukoiden tuottaminen, vaan pohdinnan kautta tuottaa suunnitteluperusteita näiden luomiseen. Vaikka tällaisten taulukoiden luonti olisikin ollut hyvä ja konkreettinen lopputulos, niin kokemus aiempien panssarivaunukalustojen osalta on osoittanut sen, että vasta käyttökokemuksen kertyessä voidaan huoltotaulukot viimeistellä. Pääasiallisena tutkimusmenetelmänä oli dokumentteihin perustuva tutkimus. Kirjallisina lähteinä olivat Suomen ja Hollannin Leopard 1- hankintasopimuksen myötä saatu tekninen dokumentaatio. Soveltuvin osin käytettiin myös Leopard 2- kaluston ja vanhempien evakuointipanssarivaunumallien käytöstä ja kunnossapidosta kertyneitä tietoja. Sekundäärimenetelmänä olivat asiantuntijahaastattelut ja avoimet lähteet. Lisähaasteen tutkimukselle toi se, että lähdemateriaali oli useaan kertaan käännetty alkuperäiskielestä. Tutkimuksen tuloksena ja johtopäätöksenä on se, että lähdemateriaalina ollut huolto-ohjelma ei suoraan sovellu käytettäväksi huolto-ohjelman luomisessa, vaan se vaatii päivittämistä soveltuakseen suomalaisiin olosuhteisiin.This thesis was made because of the need to study the topic - maintenance program for the recovery tank Leopard 1- associated with the author’s current job position. The research problem was how to develop the existing maintenance program in order to fit it into national user profile and Finnish environmental conditions, and to ensure the tank’s reliability in active use. During the pre-study work it was clear that the goal of the thesis could not be to create ready-to-use maintenance tables, but to generate a planning basis for further development through careful analysis of existing documentation. Though the creation of these kind of tables would have been a nice and concrete result, the earlier experiences with the tracked vehicles has shown that without empirical facts, the tables cannot be created. The main research method was based on documents. The documents that were acquired via the purchase contract between the Finnish and Dutch governments served as the primary source of data. Moreover, the experiences gained from the use of the Leopard 2 main battle tanks and the earlier T-55 based recovery tanks were also examined and, when applicable, used in the analysis. Expert interviews and study of open internet sources were employed as secondary research methods. An additional challenge for the study was that the source documentation was translated several times from a language to another. The conclusion of the thesis is that the original maintenance program cannot be adapted as it is but needs editing and updating in order for it to be suitable for the Finnish conditions

Pitkän sarjakuvan ymmärtäminen : työkaluja visuaaliseen tarinankerrontaan

Pitkän sarjakuvan ymmärtäminen – Työkaluja visuaaliseen tarinankerrontaan on kirjallinen opinnäytetyö, jossa sarjakuvan tekijän näkökulmasta määritellään, mitä on pitkä sarjakuva, mitkä ovat taidemuodon mahdollisuudet ja kuinka pitkää sarjakuvaa voi tehdä. Opinnäytetyössä sanallistetaan pitkän sarjakuvan erityispiirteitä visuaalisen tarinankerronnan muotona, ja sen potentiaalia esitellään pohdiskellen teoksien tarinan, hahmojen ja maailman näkökulmista. Lähdemateriaalina käytetään pitkiä sarjakuviateoksia, sarjakuvan tutkijoiden ja ammattilaisten artikkeleita, kirjoja ja muita julkaisuja sekä sarjakuvantekijän kokemusta. Pitkän sarjakuvan ymmärtäminen on kirjoitettu taiteellisen opinnäytetyön tueksi. Pitkän sarjakuvan mahdollisuuksien pohdinnasta siirrytään esittelemään erilaisia pitkän sarjakuvan tekemisen työkaluja. Pitkän sarjakuvan tekeminen on jaettu lukuihin tarinan suunnittelusta ja käsikirjoittamisesta, hahmosuunnittelusta sekä maailmanrakennuksesta. Keskeisin havainto on, että pitkän sarjakuvan erityispiirteet sopivat ennen kaikkea moniulotteisiin tarinoihin. Silti pitkän sarjakuvan tarinaan, kerrontaan tai tekemiseen ei näytä olevan valmista kaavaa, kun tarkastellaan tekijöiden ja teoksien kirjoa. Koska pitkän sarjakuvan tekeminen on monivaiheinen ja aikaa vievää tehtävä, päädytään tekijän näkökulmasta lopputulokseen, että erilaisten työkalujen kartoittaminen on kehittävää taidemuodon ja sen tekemisen hahmottamiseksi. Tulosten kautta pohditaan myös pitkän sarjakuvan tekemistä taiteellisena opinnäytetyönä.Understanding the Longform Comic – Tools for Visual Storytelling is a thesis covering a comic artist’s view on how a longform comic can be defined and created as a form of visual storytelling. This thesis discusses the characteristics and possibilities of longform comics from the different viewpoints of storytelling, characters and worldbuilding. Moving from the speculation over the potential of the art form, the thesis showcases different ways to work on longform comics. The process of making a comic is divided into sections on planning a story and scriptwriting, character creating and worldbuilding. Understanding the Longform Comic has been written to support the process of an artistic diploma. The source material includes examples of longform comics, articles, books and other forms of publications by comic researchers and professionals and the experiences of a comic artist. An essential observation is that the characteristics of longform comics are best suited for multi-dimensional stories. Still, when the wide spectrum of different longform comics and their creators are observed, there is no single pre-fabricated formula for longform comics story or process that can be identified. The connecting link between longform comics is that they are a complex and time-consuming task for artists. In order to help the longform comic artist to understand their art form, the result is to study a variety of tools for visual storytelling. A range of different methods for longform comic's creative process are described in this thesis. With the help of the collected methods, thoughts of making a longform comic as an artistic diploma work are reflected