1,720,968 research outputs found
Incretin-based therapies for the treatment of type 2 diabetes
Full text linkŠećerna bolest (ŠB) jedan je od glavnih javnozdravstvenih problema koji prerasta u pandemiju. Prevalencija šećerne bolesti tipa 2 (ŠBT2) u značajnom je porastu u mlađoj populaciji, na što utječe porast pretilosti. Osam je temeljnih patofizioloških poremećaja, koji se obično nazivaju "Omniozni oktet", uključeno u patogenezu ŠBT2. Osnovna terapija ŠBT2 podrazumijeva promjenu životnog stila uz metformin kao antidijabetik prve linije terapije. Terapija druge linije podrazumijeva dodatak drugog oralnog antidijabetika, agonista receptora glukagonu sličnog peptida 1 (GLP-1R) ili inzulina. Sveobuhvatnija definicija uspješnosti liječenja u bolesnika sa ŠBT2 uključuje usporavanje ili zaustavljanje progresije bolesti te redukciju svih čimbenika rizika koji su povezani s mikrovaskularnim i makrovaskularnim komplikacijama (hipertenzija, pretilost, hiperlipidemija, upala). U liječenju ŠBT2 preferiraju se antidijabetici koji osim svog učinka na smanjenje razine glikiranog hemoglobina (HbA1c), imaju izravne pozitivne učinke na druge faktore kardiovaskularnog rizika i nizak rizik od hipoglikemija. Inkretini su nova inovativna terapijska opcija koja uključuje agoniste GLP-1R i inhibitore dipeptidil peptidaze-4 (DPP-4). Ovi antidijabetici imaju brojne pozitivne učinke na više mehanizama uključenih u patofiziologiju ŠBT2, uključujući smanjenje tjelesne mase, krvnog tlaka, povoljni učinak na lipidni profil, potencijalni regenerativni učinak na β stanice i nizak rizik od hipoglikemije. Od velike je važnosti dokazani kardioprotektivni učinak nekih agonista GLP-1R.Diabetes is a major public health problem and is emerging as a pandemic. The prevalence of type 2 diabetes (DMT2) is significantly increasing in younger population, which is affected by obesity worldwide. There are eight core defects implicated in the pathogenesis of DMT2 commonly called the “Ominous Octet”. Pharmacologic therapy of DMT2 has changed dramatically in the last 10 years, with new drugs and drug classes becoming available. The cornerstone of diabetes therapy considers lifestyle changes with metformine added in the first line medication therapy. The second line therapy considers addition of second oral agent, GLP-1R agonist or insulin. A more comprehensive definition of treatment success in patients with DMT2 should include slowing or stopping disease progression and the reduction of all risk factors associated with microvascular and macrovascular diabetic complications (hypertension, obesity, hyperlipidemia, inflammation). We prefer antidiabetic drugs with direct positive impact on other cardiovascular risk factors not only on reducing glycated hemoglobin (HbA1c) and the ones with low risk of hypoglycemia. Incretins are a new innovative therapeutic option that includes GLP-1R agonists and DPP-4 inhibitors. These antidiabetic agents have a number of positive effects on multiple mechanisms involved in pathophysiology of the T2DM, including weight loss, reduction of blood pressure, beneficial effect on the lipid profile, potential regenerative effect on beta cells, and low risk of hypoglycaemia. Of great significance is the proven cardioprotective effect of some GLP-1R agonists
Biochemical markers of myocardial ischemia
No full textOtkrivanje reverzibilne ishemije prije razvoja ireverzibilne nekroze miokarda je
veliki dijagnostički i terapijski izazov. Ukoliko bi se prolazna ishemija mogla otkriti
biokemijski, rana terapijska intervencija mogla bi spriječiti progresiju do mionekroze.
Oko 40 % bolesnika s akutnim koronarnim sindromom (AKS) ne razvije nekrozu
unatoč izraženoj koronarnoj bolesti i kardijalnoj ishemiji. Sekvencijsko određivanje
troponina uz snimanje elektrokardiograma (EKG) vrlo je osjetljiva metoda za
dijagnostiku infarkta miokarda, ali ne i za prepoznavanje ishemije. Stoga je razumljiva
znanstvena težnja za otkrivanjem ranog markera ishemije miokarda mjerljivog prije
razvoja nekroze koju danas otkrivamo porastom troponina tek nakon četiri sata.
Dosadašnja istraživanja ističu nekoliko različitih markera kojima je zajednička
osobina promptni porast u ishemijskom okruženju (pet minuta do tri sata) te brz
povratak na normalu (tri do 24 sata). Najperspektivnijim se čine ishemijom
modificirani albumin (IMA), glikogen fosforilaza izoenzim BB (GPBB), nevezane
slobodne masne kiseline (FFAU) i njihov specifični srčani protein koji veže masne
kiseline (H-FABP), kolin i kopeptin. Uvođenje biokemijskih markera ishemije
miokarda u kliničku praksu zahtijeva dodatnu evaluaciju. Za većinu ne postoje
standardizirani analitički postupci, istraživanja za referentne intervale, niti ujednačene
kliničke evaluacije. Uz to, nespecifični su za miokard budući da i druga ishemijom
zahvaćena tkiva mogu biti izvorište navedenih markera. Zbog svega toga je njihova
vrijednost u otkrivanju ishemije miokarda ograničena i za sada nisu primjenjivi u
rutinskoj kliničkoj praksi.Diagnosis of reversible ischaemia before the development of irreversible
necrosis of myocytes is a great diagnostic and therapeutic challenge. If transient
ischemia could be detected biochemically, early therapeutic intervention could stop
progression of myonecrosis. Approximately 40% of patients with ACS does not
develop necrosis despite severe coronary artery disease and myocardial ischaemia.
The combination of serial troponin levels and ECG are very sensitive markers for
detection of myocardial infarction, but they do not detect ischemia. Therefore, there is
a reasonable scientific tendency to reveal markers which could reliably detect
ischaemia even in the absence of necrosis which is diagnosed as late as after four
hours by troponin level increase. Several biomarkers currently under investigation
tend to be short-lived, increase promptly or within 3 h, and return to reference value
within 3-24 h. The most promising of them are ischemia-modified albumin (IMA),
glycogen phosphorylase BB (GPBB), unbound free fatty acid (FFAU) and their
intracellular binding protein, heart-type fatty acid-binding protein (H-FABP), choline
and copeptin. However, their application in the clinic requires further evaluation. Most
of them are not standardized lab tests, lack reference interval evaluations or
consistent assay validation. Moreover, none of them is specific to the myocardium
since other organs can also be the origin of these biomarkers. Therefore, their use
in detecting ischemia is limited. At present, none of these biomarkers are appropriate
for routine clinical use
Amiodarone and thyroid dysfunction
Full text linkŠtitna žlijezda zauzima ključno mjesto u održavanju homeostaze cijeloga organizma. Temeljni hormon koji luči je tiroksin (T4), a učinak se dominantno ostvaruje nakon intracelularne konverzije T4 u aktivniji oblik, trijodtironin (T3), koji pokazuje veći afinitet za receptorski kompleks te time modificira gensku ekspresiju ciljnih stanica. Amiodaron je jedan od najčešće korištenih antiaritmika i upotrebljava se u liječenju širokog spektra aritmija, najčešće tahiaritmija. U svom sastavu sadrži veliki udio joda, što je, uz intrinzični učinak lijeka, temelj utjecaja na tiroidnu funkciju. Smatra se kako 15-20% bolesnika liječenih amiodaronom razvija neki oblik tiroidne disfunkcije. Amiodaron može biti uzrokom razvoja amiodaronom inducirane hipotireoze - AIH (eng.
amiodarone induced hypothyroidism) ili tireotoksikoze – AIT (eng. amiodarone induced thyrotoxicosis). AIT se češće razvija u područjima sa smanjenim, dok se AIH razvija u područjima s dovoljnim unosom joda. Tip 1 AIT češći je u bolesnika s podležećom tiroidnom patologijom, najčešće nodoznom strumom ili latentnom Gravesovom (Basedowljevom) bolešću, dok se tip 2 najčešće razvija u prethodno zdravoj štitnjači. AIH je znatno češća u bolesnika s otprije poznatim Hashimotovim tiroiditisom. Opisani su i miješani oblici bolesti. Bolesnike liječene amiodaronom potrebno je redovito pratiti, laboratorijski i klinički, kako bi se pravovremeno otkrila bilo kakva odstupanja u tiroidnoj funkciji. Temelj liječenja AIH-a je nadomjesna terapija levotiroksinom. Često u tim slučajevima nije potrebno izostavljati amiodaron iz terapije. AIT tipa 1 liječi se tireostaticima kao i ostale tireotoksikoze. Ukoliko je to moguće, preporuča se prekinuti podležeća amiodaronska terapija. Nasuprot AIT tipa 1, čiji je temeljni patofiziološki supstrat povećana sinteza i otpuštanje tiroidnih hormona, u AIT tipu 2 osnova je destruktivni tiroiditis uzrokovan amiodaronom, dezetilamiodaronom (DEA) kao njegovim glavnim metabolitom i povećanim unosom joda. Osnova liječenja tog tipa bolesti je glukokortikoidna terapija.The thyroid gland has a key role in maintaining the body's homeostasis. Thyroxine (T4) is the main hormone secreted from the thyroid gland, its effect being predominantly achieved after the intracellular conversion of thyroxine to triiodothyronine (T3), which exhibits a higher affinity for the receptor complex, thus modifying gene expression of the target cells. Amiodarone is one of the most commonly used antiarrhythmics and is used in the treatment of a broad spectrum of arrhythmias, usually tachyarrhythmias. Amiodarone contains a large proportion of iodine, which is, in addition to the intrinsic effect of the medication, the basis of the impact on thyroid function. It is believed that 15-20% of patients treated with amiodarone develop some form of thyroid dysfunction. Amiodarone may cause amiodarone-induced hypothyroidism (AIH) or thyrotoxicosis – AIT (amiodarone induced thyrotoxicosis). AIT is usually developed in the areas with too low uptake of iodine, while AIH is developed in the areas where there is a sufficient iodine uptake. Type 1 AIT is more common among the patients with an underlying thyroid pathology, such as nodular goiter or Graves (Basedow) disease, while Type 2 mostly develops in a previously healthy thyroid. AIH is more common in patients with the from before diagnosed Hashimoto's thyroiditis. Combined types of diseases have also been described. Patients treated with amiodarone should be monitored regularly, including laboratory testing and clinical examinations, to early detect any deviations in the functioning of a thyroid gland. Supplementary levothyroxine therapy is the basis for the AIH treatment. Often, in such cases it is not necessary to cease the amiodarone therapy. Type 1 AIT is treated as any other type of thyrotoxicosis, with thyreostatics. If possible, the underlying amiodarone therapy should be discontinued. In contrast to the Type 1 AIT, whose basic pathophysiological substrate is the increased synthesis and release of thyroid hormones, the basis of the Type 2 AIT is a destructive thyroiditis caused by amiodarone, desethylamiodarone (DEA) as its main metabolite and an increased iodine uptake. Glucocorticoid therapy represents the basis for treatment of this type of disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
