All posts by karin.ljubicc@gmail.com

Understanding Information

It is my great pleasure to announce the book “Understanding Information – From the Big Bang to Big Data” (link). The motivation of this book is to understand  the subject of information from many different perspectives.  The book includes contributions ranging from biology, neuroscience, computer science, artificial intelligence, quantum physics, big data, information society and philosophy. I would like to say many thanks to the respected editor Dr. Schuster from Tokyo for an invitation to contribute to this amazing and futuristic work. It was an honor to experience that sort of commitment and creative feedback. Our contribution covers the potential of plants and seeds in DNA-based information storage;full description of the experiment and its futuristic applications.

Ford Challenge Prague, 29.7. 2017

It was a challenging triathlon in the center and on the outskirts of the, so called, the most beautiful city in the hearth of Europe. On the race morning, the sun was already high in the sky and was announcing one hot day in the city. The temperatures were rising and the race was due to start at noon. We tried to get some good sleep the previous night but we had some loud Chinese neighbors who were very talkative in the morning hours. After breakfast we prepared our bikes and took a one mile stroll down to the center.

Swim start in Vltava (source: Challenge Prague)

The swim was held in the Vltava river with refreshing 17 degrees. The first impression was amazing though the water is not clean and there is some rubbish swimming allover. Anyway, through my goggles I was able to see nothing, not even my hand in front of me. The swim start was explosive and it took me by surprise while I was still polishing my goggles. It was time to start swimming. We took two U-turns and swam under two bridges. First part of the swim was against the flow and it felt harder than the other part going in the opposite direction.

Swim start in Vltava (source: Challenge Prague)

After coming out of the muddy river bank, we were getting ready for the bike part. The transition was busy and you had to took the stairs up on the bridge to get your bicycle. Cycling was held on the highways and country roads outside Prague. There were two laps to be ridden and the heat was already taking its toll. We tried to drink a lot and one big banana was my energy provider.  It was nice but I could not wait for the run to start because I did not manage to get the optimal cycling training distance in the previous months. I was counting on some experience from the past three years.

The cycling part (Source: Challenge Prague)

Finally, the running part. It is a part when you can relax knowing that somehow you will probably manage to get to the finish line. I enjoyed running and whenever there was a chance I took some watermelon for refreshment. The evening was approaching and it was time to pass the finish line. I always get emotional when this happens because you never know when your last amazing triathlon finish line will be passed. Therefore, not even one should be taken for granted.

My darling”s legendary picture. Dušan and I were too fast to be caught on tape… 🙂 (Source: Challenge Prague)

Afterwards… pizza, salmon, salad and a glass of local beer. It was a mild beer with a gentle taste, especially appropriate for women. 🙂 Though I rarely drink it and I am not really familiar with European beers. For dessert… an ice cream and one long, deep sleep. I guess we finally deserved it… the Chinese were quiet.

Finisher medals (Source: Challenge Prague)

Napredne metode zdravljenja hemofilije

Sicer mi področje ni ravno blizu, a ker se je bilo v zadnjem meecu potrebno nekoliko poglobiti v teorijo genskega zdravljenja, tukaj nekaj o naprednih metodah zdravljenja hemofilije, o katerih pred leti v študentskih knjigah ni bilo ne duha ne sluha.  Hemofilija je recesivno dedna bolezen, ki nastopi zaradi pomanjkanja specifičnega faktorja strjevanja krvi, pri kateri nastanejo same od sebe ali po neznatni poškodbi krvavitve v koži, mišicah, sklepih, dlesnih, jeziku, telesnih votlinah in krvavitve iz sečil. Ločimo dve po vzroku različni obliki hemofilije, ki se dedujeta recesivno preko kromosoma X, in sicer hemofilijo A, ki nastane zaradi pomanjkljive aktivnosti faktorja VIII (antihemofilnega globulina), in hemofilijo B, ki je posledica pomanjkljive aktivnosti faktorja IX (Christmasovega faktorja).

Source: nature.com

Pomemben napredek v zdravljenju hemofilije predstavlja genska terapija. Glavni namen genske terapije je popravek oziroma zamenjava problematične genske sekvence z namenom, da se prepreči manifestacija patološkega fenotipa. Fokus večine današnjih genskih terapija je dodajanje neokvarjenega gena brez odstranitve oz. deaktivacije okvarjenega gena. Hemofilija A in B sta med najbolj raziskanimi boleznimi za genetsko zdravljenje. Gre za in vivo prenos gena v jetra preko AAV (adeno-associated viral) vektorjev. AAV vektorji so transgenski produkti, pridobljeni s pomočjo parvovirusov. AAV vektor ima tropizem za številna tarčna tkiva, med njimi tudi jetra in skeletne mišice. Edina prava omejitev omenjenih vektorjev je, da ne morejo “nositi” sekvenc, ki so daljše od 5 kilobaznih parov. AAV ima kratko, enojnovijačno, krožno DNK molekulo, ki kodira kapsido in drug strukturne proteine virusa, hkrati pa kodira tudi proteine, ki spodbudijo integracijo virusa v specifično okvarjeno mesto na kromosomu 19. Doslej so aplikacijo AAV v človeški prganizem poskušali intravenozno (cilj jetra) in intramuskularno (skeletne mišice). Metode dostave so bile torej ali z intramuskularno injekcijo ali preko portalne ali periferne vene. Ker imamo na voljo več serotipov AAV vektorjev, lahko vplivamo na tropizem injiciranih vektorjev. Tako lahko pojasnimo dejstvo, da je aplikacija serotipa AAV8 preko periferne vene povsem učinkovita zaradi močnega hepatotropizma navedenega serotipa. Ko AAV vektorji enkrat dosežejo svoj cilj, katerega prepoznajo po serotipsko specifičnih membranskih receptorjih, z endocitotskimi vezikli vstopijo v notranjost celice. Kapsida se odstrani in nukleinska kislina vstopi v celično jedro. Nukleinska kislina nato perzistira v jedru. Pri visokih dozirnih koncentracija pride do integracije v gostiteljev genom. Doslej je bilo objavljeno eno poročilo o razvoju hepatocelularnega karcinoma pri miškah, katerim so injicirali AAV. Zdravljenje z AAV vektorji je že bilo opravljeno tudi na ljudeh, in sicer za hemofilijo B v obliki intravenoznih in intramuskularnih injekcij. Koncentracije faktorja FIX v plazmi prično naraščati po 2-6 tednih, in sicer dosežejo vrednosti 2-10%. To se na prvi pogled zdi relativno malo, vendar je z vidika hemofilije že minimalen porast v aktivnosti koagulacijskega faktorja znatnega pomena. Še vedno poteka sledenje pacientov, ki so bili zdravljeni z gensko terapijo, zato zaenkrat še ni mogoče napovedati, kako dolgo povprečno traja učinek enkratne apliakcije. Po doslej znanih podatkih je pri 1/3 pacientov 3,2 leta po enojni aplikaciji vektorja v periferno veno nivo faktorja FIX še vedno med 1-5%.

Na kratko, biotehnologija je prihodnost!  🙂

ING Night Marathon Luxembourg, 27.5. 2017

Night marathon Luxembourg became almost a tradition for us since we have been there already in 2015…and want to participate also in 2018.  It is a really lovely marathon with approximately 10.000 participants all over the world.. We flew to Luxembourg City two days before the event. First, there was an all-night drive from Maribor to Vienna with no remarkable sleep at all. During the second flight from Zurich the tiredness took its toll and I can’t even recall the take-off and landing. After setting in a nice, budget hostel near the airport the only reasonable thing was to get some good afternoon sleep. We were all a bit lazy since we only made a short trip to the capital center in the evening … and even that was dedicated to Burger King. I skipped the fast-food dinner, the most basic mistake I could have made as I realized after during the marathon. The following morning we had some breakfast with a lot of carbohydrates. It was time to get to the registration point to pick up our numbers and some other important stuff.  Pasta party in the evening was delicious, they served pasta with local ingredients and some drinks. Enough food for one day.

And there it was…the marathon morning. Actually a bit different this time since the start was at 7 PM. So we were counting down the hours and spent all day long relaxing in pyjamas,  saving all the energy for the 42,2. I was starting to feel the adrenaline which gets me every time the start approaches and it is a special felling,I was happy to be there. Though something just did not feel right and it is hard to describe what exactly. Well the start was approaching and we were almost late. There was a 15 minute bus ride to the start but unfortunately we had a bus driver who obviously did not like runners and marathons. He decided to adapt the bus route by adding 90 minutes. So we were driving around Luxembourg (which would be nice in other circumstances) and  picking up Saturday walkers at every local stop. The driver decided to drop us at main station which was 6 km away from the start. So there were not many chances to get to the start on time…we had to run fast. I have never been so warmed up before the marathon. We crossed some red lights and when the police stopped us the smartest thing was to ask them for a ride. Of course they declines but meanwhile there was a bus passing and we made another sprint to catch it. Luckily, we got on the bus headed to the start.

ING Night Marathon Luxembourg-start.
(Source: luxbynight.com)

The start was crowded with runners and the time was approaching.  Iztok and I separated for some final preparations before the start but luckily met again a few seconds before in the start box. The moment when the gun goes off and there is 42 km of running into the late evening is something worth training for.  The sun was still high and the water was out of reach.  The first 10 km were the hardest… I felt mentally tired, though the legs were soft and eager to run. I must say I have never felt so low in any endurance competition till this marathon and I could easily stop and lay down somewhere in the grass by the way. But quitting is never an option. I was trying to think positively,  indulging into all the beautiful things by the way, cheering crowds and the smell and colors of a magnificent spring evening in the city of Luxembourg. I admit I had a crisis until I have reached the 15th kilometer. After that everything became easier and I was starting to feel strong and full of energy.  I focused on the finish line and the time just went by. The course was leading us through the small streets of Luxembourg, people by the way were cheering and enjoying the evening.  There was a smell of grilled food all around. Children by the way were pouring us with water and giving us “high-fives”. Truly, a lovely marathon. Really enjoyed it.

The spirit of marathon.
(Source: marathons.ahotu.com)

The sun went down and deep into the dark I started to realize that the finish line is approaching. Going into the last kilometer was emotional and full of adrenaline. Not even one finish line should not be taken for granted and therefore I really appreciate all the finishes in the past. Finish line was magnificent again and afterwards I took a few minutes to lay down on bare ground…still gathering all the impressions. This is the “runner’s high” and you eventually become addicted to it…

Hematofagocitna limfohistiocitoza (HLH)

Čeprav je v vsakdanjem delu bolje razmišljati pragmatično in se osredotočiti na najverjetnejše diagnoze (ker se pri pri pretiranem poglabljanju lahko spregleda tiste očitne “zastavice”), je včasih dobro slišati tudi o redkejših diagnozah.

Ena takšnih je hematofagocitna limfohistiocitoza, ki mi je v zadnjem mesecu zelo ostala v spominu, ker sta na enem izmed oddelkov v kratkem razmaku ležala kar dva pacienta s to diagnozo (toliko o redkosti).  Gre za nekontrolirano hipervnetno stanje, ki ga pri predisponiranih posameznikih lahko spodbudi okužba (EBV), malignom (tipično limfom) ali avtoimuna bolezen. Eden izmed teh dejavnikov spodbudi pozitivno povratno zanko intenzivnega sproščanja citokinov zaradi okvare aktivnosti citotoksićnih limfocitov T in naravnih celic ubijalk.

Na sindrom je potrebno posumiti pri perzistentnem vročinskem stanju, ki ga lahko spremlja bicitopenija, splenomegalija, povišane zaloge feritina kot marker perzistentnega vnetja in nekaj drugih kriterijev, ki so ali niso prisotni. Ime “hematofagocitna” izhaja iz procesa, ko aktivirani makrofagi “jedo” druge krvne celice, čigar posledica je citopenija. Sicer pa hematofagocitoza v razmazu ni patognomonična za sindrom. Na drugi strani pa je hiperferitinemija ena izmed karakterističnih pokazateljev, da bi ob ustrezni klinični sliki in pridruženi citopeniji lahko šlo za HLH.

Poleg zdravljenja vzroka je za umiritev citokinske nevihte potrebna imunosupresorna in imunomodulatorna terapija, še prej pa seveda posvet z revmatologom in hematologom, katera sta pravzaprav vodji zdravljenja te pogosto spregledane diagnoze.

Pomembno sporočilo je torej, da ob vročinskem stanju s citopenijo in hiperferitinemijo, predvsem pri kritičnih pacietnih v enoti intenzivne terapije, pomisliti tudi na HLH. Za nas, ki pa smo šele na začetku poti s pridobivanjem izkušenj, pa mogoče koristno  znanje za kdaj pozneje. Tukaj pa še link do brezplačnega zelo kratkega prispevka, ki pove vse o tej temi: Link.

Laguna Porec Half Marathon, 26.3. 2017

Last weekend we took part in another half marathon distance after a long, cold winter. It felt so good to wear shorts again and do the running by the sea.

We have decided to arrive two days before the run on Friday night. It was almost midnight and at the time of our arrival a nice hotelier apologized since there was no dinner left. Of course. Never mind, we were full of the world`s best cake from Iztok`s grandma. The next day we were woken up by a small, grey-yellow colored bird knocking on our window. By being so nice to wake us up, a birdy deserved a breakfast, some bread leftovers from the previous night, and soon there was a flock of few small birds and two big gulls on the front yard.

A view from Grožnjan

We decided to visit a small town of Grožnjan on Saturday. In a small local Kaufland we found a small piece of my “best-ever” cheese, a goat cheese from the Pag island. Two bites and it was gone. By the way, this cheese has received numerous awards (MIH Dairy Kolan) and it is my all time favorite. Grožnjan is actually a small settlement and it is known as the city of artists. Many houses have been reorganized into painting studios. When returning to Poreč, we registered for the run, got our numbers and went back to pick up some dinner. There was pizza, pasta, potatoes and lots of salad. I also tried some white shark meat and squids and it was more than enough.

Too cold for swimming

On the race morning we were again woken by the same bird knocking on the window. No alarm clock needed. It was time to get up, dress up and eat some breakfast. The start area was already crowded with runners, more than 800 from different parts of the world, the most distant ones came from Kenya. We did some warming up and then it was time to get started with 21 km distance in front of us. The first few kilometers of fast running felt so good, there were three 7 km laps routed by the shore. I could feel the salty sea breeze on my skin and I have decided to speed up in the second lap. I must say I was surprised with how good I felt since there was not as much time invested into training this winter as it was in previous year. The finish line was getting closer and closer, the distance just flew by. I have almost forgotten how good this feels like. Amazing day once again.

Start and finish line

We have decided to do it once again next year. It is a well organised event in a lovely setting.  The next in line is 42 km of ING Night Marathon Luxembourg. Can`t wait.

Intelligent sport training

The advent of artificial intelligence has also entered in the field of sport training. Every time we undergo a training session our sport watches collect and save different parameters, which require further analysis in order to improve our next performance. And not to mention all the parameters we are unaware of. Of course, human cognitive functions are of limited value in dealing with large data sets. Our brain might intuitively  plan the following training based only on how we felt during the past training and not regarding the actual performance facts which can only be detected with the tools of computational intelligence. There are hidden correlations to be  found.  Our past work has proven to be more than useful in this area and here you can find our articles regarding this hot topic: Planning the sports training session with the bat algorithm and Computational intelligence in sports: Challenges and opportunities within a new research domain.  The advent of a new concept in the form of artificial sport trainer in collaboration with a human trainer is still in the developing phase. Hence we could see it fully in practice in the following years.

Labelling of varieties covered by patent protection

One of practical implications of storing data into plants is an insertion of short DNA labels into protected plant varieties. It is a new approach for managing intellectual property rights in the seed industry. By using our online application tool it will become easy to distinguish protected from non-protected varieties. The original scientific article was published in Transgenic Research by Springer and is available at:

Article

WINFOCUS: Vse o uporabi UZ na enem mestu

Pretekli teden je v Ljubljani potekal 12. svetovno znani kongres posvečen ultrazvoku in širjenju njegove uporabnosti. Edinstvena priložnost, saj gre sicer za kongres, ki je vsako leto organiziran drugje v svetu, medtem ko so posamezni segmenti kongresa organizirani posamično tudi v Sloveniji. A kot rečeno, tokrat celoten WINFOCUS v Ljubljani. Udeležila sem se dvodnevnega programa uporabe ultrazvoka v vsakdanjih urgencah in resnično lahko rečem, da po skupno 12 urah predavanj in 8 urah praktičnega dela z ultrazvokom zapustiš prizorišče samozavestnejši za trenutke, ko ti na vrata urgentne ambulante potrka pacient z dispnejo in bolečino v prsnem košu. Da ne omenjam vsakdanjega kruha urgentnih ambulant – globoke venske tromboze in pljučne embolije. In v infektologiji pogosti vzrok dispneje – pljučnica s pridruženim plevralnim izlivom – vse to in še več je sposoben prepoznati soliden UZ in seveda ultrazvočist za njim. Ni zastonj namera, da bi vsak zdravnik poleg stetoskopa v žepu nosil še dlančni UZ aparat, tudi kot aplikacija s sondo na našem mobilnem telefonu.

Echocardiogram
                                                Echocardiogram

Osnovni pristop h kritično bolnemu je naš algoritmični ABCDE. In prav pri vsaki črki protokola nam pomaga ultrazvočni aparat.

Pri pregledu A(irway) si lahko z linearno sondo pomagamo pri vstavitvi endotrahealnega tubusa. Predvsem nas seveda zanima ali smo vstopili v trahejo ali v požiralnik. Druga redkejša indikacija je uporaba za lociranje tiroidnega in krikoidnega hrustanca oziroma krikotiroidne membrane, kadar je zgornja dihalna pot neprehodna. Konikotomije oziroma krikotiroidotomije nihče nerad izvaja na slepo, z UZ pa nam je prihranjena dilema pri lociranju mesta, kjer bomo pičili.

Pri pregledu B(reathing) nas zanima več stvari. Sicer je boljša uporaba linearne sonde in manjše globine, a z abdominalno sondo dobimo širše vidno polje. Zanima nas “lung sliding, lung pulse in B linije (več kot dve na en medrebrni prostor). Če je kateri izmed treh naštetih pojmov viden oziroma najden na UZ pljuč, lahko s 100% verjetnostjo ovržemo pnevmotorax tega pljučnega krila. Dodatno nam najdba “lung point”,kjer je plevra tipično prekinjena, seveda na kazuje pnevmotorax. Na drugi strani pa najden kateri izmed teh znakov ne pomeni, da je krivec pnevmotorax, saj gre lahko tudi za KOPB ali drugo dogajanje v pljučih. B linije so znak spremenjene lomljivosti svetlobe in nam nakazujejo intersticijski sindrom oziroma edem (pljučni edem katerekoli etiologije, pljučnica,…). Na bazi pljuč, kjer je diaframga v stiku z jetri desno ali vranico levo, smo pozorni na t.i. znak zavese oz “curtain sign”. Preprosto rečeno, smo pozorni ali se med mirnim dihanjem diafragma lepo pomika glede na vretenca in ali preko diafragme ne zaznamo hipoehogene tekočinske kolekcije. Sistematičen in koristen UZ prikaz pljuč je na voljo na tej povezavi: https://www.youtube.com/watch?v=uv6zI4QHYss

Pri pregledu C(irculation) je UZ izjemnega pomena. Pregledamo lahko vse tri pomembne komponente, torej vene, srce in arterije. Za oceno šokiranega bolnika po poškodbi ali mlade ženske, v šokovnem stanju, s sumom na rupturirano ektopično nosečnost, je FAST UZ pregled trebuha nepogrešljivega pomena. Pregledamo 3 (vključno s perikardialnim prostorom 4) področja v telesu, kamor bi se lahko izgubljala tekočina. In sicer desno hepatorenalno področje vključno z desnim plevralnim prostorom, levi splenorenalni žepek z levim hepatorenalnim prostorom, substernalni pogled na perikardialni ovojček in preko mehurja pogled v rektovesikalni žepek pri moškem oziroma rektovaginalni žepek pri ženski. Prosta tekočina v teh predelih nam nakaže, da je vzrok šoka lahko hipovolemija. Nazoren prikaz pa v tem videu: https://www.youtube.com/watch?v=6qWNmMvAfdQ

Dodatno lahko pregledamo tudi aorto, če sumimo na rupturo anevrizme ter za oceno volemije še polnjenost spodnje vene cave. Pregled srca sestoji iz treh pogledov, najbolje je seveda uporabljati kardiološko sondo, čeprav se da tudi z abdominalno sondo kar precej videti. Pogledamo substernalno, parasternalno in apikalno. Najboljši je parasternalni pregled. Ocenjujemo 3 E-je, in sicer “equality, ejection, effusion”. Pod prvo točko nas zanima ali je desni prekat manjši od levega, ali je septum raven. Kakršnekoli anomalije normalnih razmerij bi nam lahko nakazovale povečane polnilne tlake v desnem srcu, ki bi nastopili recimo ob pljučni emboliji, pljučni hipertenziji, ipd. Drugi pojem nam nakazuje ustreznost sistolne funkcije in kaže na možno hipotonijo srca recimo ob infarktu. Tretji pojem pa se navezuje na perikardilani izliv oziroma na morebiten hipoehogeni pas tekočine v perikardu. Prikaz pa tukaj: https://www.youtube.com/watch?v=H_3V9xlDMA0

Na koncu pregledamo še vene, katere pa sem že opisovala v enem izmed prejšnjih postov. Dvotočkovni pregled ob sumu na GVT je po raziskavah dovolj za izključitev potencialno nevarne GVT, katere ne moremo poslati domov z napotnico za UZ čez dva dneva. Prva točka pregelda je predel v. femoris communis z vtočiščem v. saphene magne. Druga točka pa je pregled poplitealne vene z v. sapheno parvo. V obeh naštetih točkah iščemo znake tromboze in skušamo stisniti vene z ultrazvočno sondo. Izvedemo lahko tudi augmentacijo, pozorni pa smo lahko tudi na respiratorni alterans z dihanjem. Vsekakor izjemnega pomena, ko se odločamo ali je oteklina na račun limfedema, površinskega tromboflebitisa ali resnično GVT.

WINFOCUS zelo priporočam v udeležbo. Ko je pred tabo resnična situacija z adrenalinom na vrhuncu in pacientom v akutni stiski, je vsako čakanje na dodatne slikovne preiskave (RTG pc. CT, ipd.) lahko preveč zamudno in je tista neškodljiva naprava v kotu sobe lahko diagnostičnega pomena.

Challenge Šamorin, Slovakia, 21.8. 2016

On 21. of August we took part in an inagural Challenge Samorin, Slovakia. It was a 1,9 km swim, 90 km bike and a half-marathon run… Swimming took part in the Donau river, which had pleasant 19 degrees. Though it was only an up and down route with no obvious turns to the left or right, it was a particulary special swim because of the current. Anyway, on the bike it started raining like a shower.  I was kind of a “deja vu”…like Iceland… again cold and wet bike ride.

Swim start (source: Challenge Šamorin)
Swim start (source: Challenge Šamorin)

Well, once we managed to get to the running part it was all OK. It was a really lovely run on the banks of the Donau river, the rain stopped and we started enjoying the countdown to the finish line. Through the rice I have been feeling rather tired and sleepy, a long season behind has started to take its toll. But still, we had a really nice time in Slovakia and the race was just a relaxation during the weekend.

Now, that is it for this season. 1 Ironman and 4 half-Ironman distances this year. I am really satisfied with the 2016 season. 🙂 Now it is time for autumn and winter… and indulging into activities other than triathlon.