Zeitschriftenartikel zum Thema „Stop kodon“

Latar belakang. Sepertiga pasien kejang demam pertama mengalami bangkitan ulang kejang demam. Riwayat keluarga adalah pernah kejang demam dan mutasi gen merupakan faktor risiko bangkitan kejang demam berulang.Tujuan. Membuktikan faktor genetik sebagai risiko terjadi kejang demam berulang.Metode. Rancangan penelitian kohort prospektif. Subjek pasien kejang demam pertama, selama 18 bulan diamati terjadi bangkitan ulang kejang demam. Amplifikasi DNA dengan teknik PCR dan sequencing untuk melihat mutasi gen pada kanal ion Natrium. Pengujian hipotesis memakai regresi logistik, dan uji korelasi memakai Rank Sperman corelation.Hasil. Sepertiga pasien kejang demam pertama mengalami kejang demam berulang. Mutasi gen kanal ion Na+ SCNIA 19(61,3%) pasien, terdapat pergantian Argenin (R) oleh asam glutamat (Glu) (Arg1627Glu) (mutasi missense) dan kodon stop (TGA).(mutasi nonsense), sedangkan pada SCNIB 12(38,7%) pasien, terdapat mutasi heterozigot, yaitu kodon 130:GAA /AAA, kodon 96:CGG/TGG, kodon 138:GTC/ATC, kodon 95:AGC /ATT dan kodon:154 GCT/AAT. Ada hubungan mutasi gen dengan umur, suhu dan riwayat keluarga pernah kejang demam, saat kejang pertama. (koefisien korelasi berturut-turut –0,359; -0,339; 0,278). Riwayat keluarga pernah kejang demam dan mutasi gen berisiko 2-3 kali terjadi kejang demam berulang (RR 2.9, p<0,05 dan RR 3.556 p>0,05)Kesimpulan. Sepertiga pasien kejang demam pertama mengalami kejang demam berulang. Riwayat keluarga pernah kejang demam dan mutasi gen merupakan faktor risiko kejang demam berulang. Terdapat hubungan mutasi gen dengan umur, suhu dan riwayat keluarga pernah kejang demam, saat kejang pertama

V delu smo izvedli analizo optimizacije procesa obdelave umetniškega lesenega izdelka (okvir ogledala) na 3-osnem CNC stroju. Iz grafične slike smo najprej v programu ArtCAM izdelali 3D model, triangulirali njegovo površino in ustvarili STL datoteko. To smo naložili v program SolidWorks, kjer smo z njegovim dodatkom SolidCAM določili parametre obdelave. Grobo obdelavo smo določili z operacijami HSR (high speed roughing), fino pa s HSM (high speed machining). Posamezne operacije smo primerjali in ugotovili, da bi najkrajši čas obdelave pri najboljši kvaliteti dobili pri izbiri HSR operacij »Contour Roughing«nato »Rest Roughing« ter HSM operacije »3D Constant Step Over«, znašal pa bi 4 ure in 1 minuto. Izdelano kodo smo preverili s simulacijo izdelave ter na koncu izdelali G kodo za naš izdelek.

Zespół Imerslund-Gräsbecka (Imerslund-Grasbeck syndrome, IGS, zaburzenie wchłaniania jelitowego kobalaminy) jest rzadką autosomalną chorobą recesywą występującą u psów oraz ludzi. Przyczyną IGS są mutacje genów CUBM lub AMN, które kodują białka będące podjednostkami kompleksu receptorowego kubilina–amnionlessyna, odpowiedzialnego za wchłanianie kobalaminy (wit. B12) w jelicie cienkim. Najczęściej przyczyną choroby jest mutacja c.786delC lub c.8392delC w genie CUBM, w wyniku której dochodzi do przesunięcia ramki odczytu, powstania przedwczesnego kodonu STOP, a w konsekwencji degradacji mRNA. Zespół zidentyfikowano u różnych ras psów, m.in. border collie, owczarków australijskich i sznaucerów olbrzymich. Objawy kliniczne występują u młodych psów i obserwowane są ok. 8–12 tygodnia życia ze względu na wyczerpanie zapasów witaminy B12 w wątrobie. Pierwszymi objawami IGS są utrata apetytu oraz nieprawidłowy rozwój szczeniąt powiązany z niedokrwistością oraz białkomoczem.

Development of phytopharmaca for cancer until now has become a major step in overcoming the failure of cancer therapy. Calotrophis gigantea is one of the scientifically proven plants both in vitro and in vivo as a chemopreventive agent. This study aims to explain the efficacy and safety of Calotropis gigantea leaf extract (EDCG) and Calotropis gigantea root extract (EACG) on NIH3T3 cell, colon cancer cell WiDr and T47D breast cancer cells. From the analysis of MTT and Selectivity Index (SI) analysis showed that ethanol extract of leaf Calotropis gigantea (EDCG) can inhibit selective growth of selective colon cancer cells (SI 3) but not selective in inhibiting the growth of breast cancer cells T47D (SI 3 ). Calotropic gigantea (EACG) root ethanol extract is not selective in inhibiting the growth of colon cancer cells WiDr and breast cancer cells T47D (SI 3). Therefore EDCG can be recommended as a Phytopharmaca candidate with further proof through clinical trials.

Background:Loss of articular cartilage is one of the major signs of osteoarthritis (OA). Aggrecan, the main proteoglycan component of the extracellular matrix of articular cartilage is cleaved by ADAMTS-5 (A Disintegrin And Metalloproteinase with ThromboSpondin-motif-5).1GLPG1972/S201086, a potent and highly selective inhibitor of ADAMTS-5, is an oral Disease-Modifying OsteoArthritis Drug (DMOAD) candidate. In a pooled Phase 1 safety analysis involving 171 participants GLPG1972/S201086 was shown to be well tolerated.Objectives:To present the study design of ROCCELLA, a large Phase 2 clinical trial in knee OA (KOA) patients, evaluating the efficacy and safety of GLPG1972/S201086 in reducing cartilage loss in OA.Methods:ROCCELLA is a multinational 52-week, multicentre randomized double-blind placebo-controlled dose-ranging phase 2 trial for the treatment of OA (NCT03595618). Eligible patients were aged 40–75 years with a diagnosis of primary femorotibial KOA, a pain score of 40–90mm on a 100 mm Visual Analogue Scale (VAS), predominant medial disease and a combined Kellgren/Lawrence (KL) 2 or 3 and Osteoarthritis Research Society International (OARSI) medial joint space narrowing (JSN) 1 or 2 severity grading range upon central reading of the X-ray. If both knees were eligible, the target knee was selected based first on the highest KL grade, then on the highest JSN grade and finally on the highest pain VAS score at baseline. Patients were randomized 1:1:1:1 to take placebo or three dose levels of GLPG1972/S201086 orally once daily for 52 weeks. The target knee was evaluated by quantitative Magnetic Resonance Imaging (qMRI) at baseline visit, week 28 and week 52, or at early withdrawal.The primary endpoint of the study is change from baseline to week 52 in cartilage thickness of the central medial tibio-femoral compartment (cMTFC) of the target knee. Secondary objectives are safety and tolerability including treatment emergent serious adverse events. Additional secondary structural and clinical efficacy objectives are based on changes from baseline in the target knee: cartilage thickness and bone area on qMRI, KOA “progressor” rates, Joint Space Width on X-ray, pain VAS, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total and sub scores, Patient Global Assessment VAS and the proportion of Outcome Measures in Rheumatology (OMERACT)-OARSI responders. Blood will be collected to assess the pharmacokinetics of GLPG1972/S201086. Planned, exploratory analyses include biochemical biomarkers of cartilage and bone turn-over. The study is designed to maintain the experiment wise type I error at 5%. A Mixed-effects Model for Repeated Measures will be used for the primary analysis. The randomisation was stratified by geographic region.Results:The study started in August 2018 and was fully recruited (N=938) by June 2019. Large numbers of patients with KOA had to be screened to meet the stringent pre-specified selection criteria. The study completion is expected by end of 2020.Conclusion:This is the first large Phase 2 study where patients with primary KOA are treated for 52 weeks with GLPG1972/S201086, an orally administered DMOAD candidate. This clinical trial was designed with a combination of two radiological selection criteria to ensure sufficient structural progression (cartilage loss) in the study population.References:[1]Durigova Met al.Osteoarthritis Cartilage2008;16:1245–52.Acknowledgments:This study was funded by Galapagos NV. Editorial support was provided by Oxford PharmaGenesis and funded by Galapagos NV.Disclosure of Interests:Henri Deckx Employee of: Galapagos, Ellen van der Aar Employee of: Galapagos, Marjolijne van der Stoep Employee of: Galapagos, Marianne Wooning Employee of: Galapagos NV, Katy Bernard Employee of: Institut de Recherches Internationales Servier, Sergey GRANKOV Employee of: Institut de Recherches Internationales Servier, Olivier Imbert Employee of: Institut de Recherches Internationales Servier, Maria Pueyo Employee of: Institut de Recherches Internationales Servier, Felix Eckstein Grant/research support from: Merck, Orthotrphix, Servier, Galapagos, Kolon Tissuegene, Samumed, Novartis, Consultant of: Merck, Bioclinica, Servier, Samumed, Roche, Kolon Tissuegene, Galapagos and Novartis, Employee of: co-owner and employment with Chondrometrics

Recently, Nutrition Support Teams (NSTs) has been spreading throughout Japan. Nutritional assessment is important as an initial step among NST activities, since the patients can be identified based on this assessment whether they needs supports by NST or not. Serum trace element is one of the most useful and convenient nutritional indices. The aim of this study is to analyze the relationships between serum trace element values and clinical backgrounds in NST patients by data mining. The subjects of this study consisted of 29 NST patients who were admitted to our hospital between January 2005 and October 2006. Serum trace elements in patients were analyzed by PIXE method. The data were analyzed by a data mining software, i.e. "ICONS Miner" (Koden Industry Co., Ltd.). The significant "if-then rules" were extracted from the decision trees. The target variable of the decision trees is whether nutritional conditions of the patients are improved or not (Yes/No). The explanatory variables of the decision trees are the values in serum trace elements (Fe, Cu, Zn, Se, Mn) and TTR (transthyretin). The analyses demonstrated that the first node of the decision tree was Zn. Therefore, serum Zn value might be the most significant factor among these trace elements in estimating the improvement of nutritional conditions of the patients. In the decision, the second branch was the Fe value, and the Cu the third. The following significant "If-then rules" were extracted from the decision trees. If-then rule 1: If serum Zn value >758.6 µg/l, then improvement of nutritional condition = Y. (1.00 = 9/9) If-then rule 2: If serum Zn value ≤758.6 µg/l and Fe ≤653.2 µg/l and Cu ≤682.5 µg/l, then improvement of nutritional condition = Y. (1.00 = 5/5) If-then rule 3: If serum Zn value ≤758.6 µg/l and Fe ≤653.2 µg/l and Cu >682.5 µg/l and Se >119.8 µg/l, then improvement of nutritional condition = Y. (1.00 = 3/3) In conclusion, data mining analysis of serum trace elements was found to be an effective method in assessing the nutritional conditions in NST patients.

Background:Osteoarthritis (OA) is a degenerative joint disease involving structural pathology of all joint tissues, and most commonly affecting the knee, hip and hand. Degradation of the cartilage extracellular matrix represents a central feature of OA and is widely thought to be mediated by proteinases that degrade primarily aggrecan and collagen. ADAMTS-5, a Disintegrin And Metalloproteinase with ThromboSpondin-motif-5, is a key aggrecan-cleaving enzyme involved in cartilage degradation. S201086/GLPG1972, a potent and highly selective inhibitor of ADAMTS-5, is an oral Disease-Modifying OsteoArthritis Drug (DMOAD) candidate.Objectives:The primary objective of the ROCCELLA phase 2 clinical trial (NCT03595618) is to evaluate the effect of S201086/GLPG1972 over 52 weeks of treatment (3 dose groups compared to placebo) in reducing cartilage loss. Cartilage thickness of the knee is being measured quantitatively by Magnetic Resonance Imaging. Here, we describe the baseline characteristics of patients included in the ROCCELLA clinical trial.Methods:The main inclusion criteria were: male or female, aged 40 to 75, with a diagnosis of knee OA according to the clinical and radiological criteria of the American College of Rheumatology. The target knee had to meet a pain score between 40 and 90 mm on a 100 mm Visual Analog Scale (VAS), and the following radiographic feature upon central radiographic readings: Kellgren/Lawrence (KL) 2 or 3 and OARSI medial joint space narrowing (JSN) 1 or 2 (for more details see Deckxet al. OARSI 2020). The rationale for these specific radiographic inclusion criteria was to ensure sufficient cartilage loss over 12 months to assess the efficacy of S201086/GLPG1972.Results:Across 12 countries, 3319 patients were screened and 932 were finally included in the study. The screen failure of 72% is mainly due to the radiological criteria. The age of the patients was 62.9 ± 7.3 years (mean ± SD) with a majority of women (69.3%). The BMI was 30.5 ± 4.7 kg/m2. The duration of knee OA was 7.2 ± 6.9 years. Five hundred and one (53.8%) patients reported a medical history of musculoskeletal and connective tissue disorders, mainly osteoarthritis in other sites (20.2%), back pain (13.6%), and arthralgia (9.8%). At inclusion, 97.2% of the patients were taking different types of drug treatments, mainly anti-inflammatory and anti-rheumatic products (69.4%) and analgesics (42%). At baseline, 11% of the target knees were KL2 and 89% were KL3; 32% were OARSI medial JSN grade 1 and 68% grade 2. Target knees at inclusion had a pain score on the VAS of 63.5 ± 11.4 mm (range 0-100, with 0 for no and 100 for extreme pain) and a total WOMAC (Likert 3.1) score of 48.0 ± 15.0 (range 0-96). The WOMAC subscores for pain, stiffness and physical function were 10.0 ± 3.2 (range 0-20), 4.2 ± 1.6 (range 0-8) and 33.8 ± 11.2 (range 0-68, indicating functional limitation), respectively.Conclusion:For this clinical trial, patients were selected to present radiological criteria (i.e.OARSI JSN 1 and 2) to ensure sufficient structural progression (cartilage loss) over 12 months, as well as clinical symptoms. These stringent selection criteria were the main cause for the high screen failure rate. These baseline characteristics should warrant the ability to evaluate the efficacy of S201086/GLPG1972 as a DMOAD candidate. The search for an effective pharmacological treatment that can prevent or cure OA remains a major challenge and unmet medical need.Disclosure of Interests:Katy Bernard Employee of: Institut de Recherches Internationales Servier, Sergey GRANKOV Employee of: Institut de Recherches Internationales Servier, Marjolijne van der Stoep Employee of: Galapagos, Agnès Lalande Employee of: Institut de Recherches Internationales Servier, Olivier Imbert Employee of: Institut de Recherches Internationales Servier, De Phung Employee of: Galapagos, Damien Chimits Employee of: Institut de Recherches Internationales Servier, Karine Muller Employee of: Galapagos, Ellen van der Aar Employee of: Galapagos, Henri Deckx Employee of: Galapagos, Maria Pueyo Employee of: Institut de Recherches Internationales Servier, Felix Eckstein Grant/research support from: Merck, Orthotrphix, Servier, Galapagos, Kolon Tissuegene, Samumed, Novartis, Consultant of: Merck, Bioclinica, Servier, Samumed, Roche, Kolon Tissuegene, Galapagos and Novartis, Employee of: co-owner and employment with Chondrometrics

Optical Coherence Imaging (OCI) including Optical Coherence Tomography (OCT) and Optical Coherence Microscopy (OCM) uses interferometric detection to generate high-resolution volumetric images of the sample at high speeds. Such capabilities are significant for in vivo imaging, including ophthalmology, brain, intravascular imaging, as well as endoscopic examination. Instrumentation and software development allowed to create many clinical instruments. Nevertheless, most of OCI setups scan the incident light laterally. Hence, OCI can be further extended by wide-field illumination and detection. This approach, however, is very susceptible to the so-called crosstalk-generated noise. Here, we describe our novel approach to overcome this issue with spatio-temporal optical coherence manipulation (STOC), which employs spatial phase modulation of the incident light. Full Text: PDF ReferencesL. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, "Ballistic 2-D Imaging Through Scattering Walls Using an Ultrafast Optical Kerr Gate", Science 253, 769-771 (1991). CrossRef D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et al., "Optical coherence tomography", Science 254, 1178-1181 (1991). CrossRef J. A. Izatt, E. A. Swanson, J. G. Fujimoto, M. R. Hee, and G. M. Owen, "Optical coherence microscopy in scattering media", Opt. Lett. 19, 590-592 (1994). CrossRef D. Borycki, M. Nowakowski, and M. Wojtkowski, "Control of the optical field coherence by spatiotemporal light modulation", Opt. Lett. 38, 4817-4820 (2013). CrossRef D. Borycki, M. Hamkalo, M. Nowakowski, M. Szkulmowski, and M. Wojtkowski, "Spatiotemporal optical coherence (STOC) manipulation suppresses coherent cross-talk in full-field swept-source optical coherence tomography", Biomed. Opt. Express 10, 2032-2054 (2019). CrossRef P. Stremplewski, E. Auksorius, P. Wnuk, L. Kozon, P. Garstecki, and M. Wojtkowski, "In vivo volumetric imaging by crosstalk-free full-field OCT", Optica 6, 608-617 (2019). CrossRef L. Vabre, A. Dubois, and A. C. Boccara, "Thermal-light full-field optical coherence tomography", Opt. Lett. 27, 530-532 (2002). CrossRef M. Laubscher, M. Ducros, B. Karamata, T. Lasser, and R. Salathé, "Video-rate three-dimensional optical coherence tomography", Opt. Express 10, 429-435 (2002). CrossRef Dubois and A. C. Boccara, Full-Field Optical Coherence Tomography, (Springer Berlin Heidelberg, Berlin, Heidelberg, 2008), pp. 565-591. CrossRef O. Thouvenin, K. Grieve, P. Xiao, C. Apelian, and A. C. Boccara, "En face coherence microscopy [Invited]", Biomedical Opt. Express 8, 622-639 (2017). CrossRef F. Fercher, C. K. Hitzenberger, M. Sticker, E. Moreno-Barriuso, R. Leitgeb, W. Drexler, and H. Sattmann, "A thermal light source technique for optical coherence tomography", Optics Commun. 185, 57-64 (2000). CrossRef R. A. Leitgeb, "En face optical coherence tomography: a technology review [Invited]", Biomed Opt Express 10, 2177-2201 (2019). CrossRef J. Fujimoto and W. Drexler, Introduction to Optical Coherence Tomography, (Springer, Berlin, Heidelberg, 2008), pp. 1-45. CrossRef J. A. Izatt, M. A. Choma, and A.-H. Dhalla, Theory of Optical Coherence Tomography, (Springer International Publishing, Cham, 2015), pp. 65-94. CrossRef

<b>Introduction:</b> Endoscopic full-thickness resection (EFTR) is a powerful option for resection of colorectal lesions not amenable to conventional endoscopic resection. The full-thickness resection device (FTRD) allows clip-assisted EFTR with a single-step technique. We report on results of a large nationwide FTRD registry. <b>Methods:</b> The «German colonic FTRD registry» was created to further assess efficacy and safety of the FTRD System after approval in Europe. Data were analyzed retrospectively. <b>Results:</b> Sixty-five centers contributed 1,178 colorectal FTRD procedures. Indications for EFTR were difficult adenomas (67.1%), early carcinomas (18.4%), subepithelial tumors (6.8%), and diagnostic EFTR (1.3%). Mean lesion size was 15 × 15 mm and most lesions were pretreated endoscopically (54.1%). Technical success was 88.2% and R0 resection was achieved in 80.0%. R0 resection was significantly higher for subepithelial tumor compared with that for other lesions. No difference in R0 resection was found for smaller vs larger lesions or for colonic vs rectal procedures. Adverse events occurred in 12.1% (3.1% major events and 2.0% required surgical treatment). Endoscopic follow-up was available in 58.0% and showed residual/recurrent lesions in 13.5%, which could be managed endoscopically in most cases (77.2%). <b>Discussion:</b> To date, this is the largest study of colorectal EFTR using the FTRD System. The study demonstrated favorable efficacy and safety for «difficult-to-resect» colorectal lesions and confirms results of previous studies in a large «real-world» setting. Further studies are needed to compare EFTR with other advanced resection techniques and evaluate long-term outcome.