Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis. Here, we discovered a molecule (M47) that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The M47 selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and resulted in increasing the circadian period length of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 increased degradation of the CRY1 in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced oxaliplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Systemic repetitive administration of M47 increased the median lifespan of p53−/− mice by ~25%. Collectively our data suggest that M47 is a promising molecule to treat forms of cancer depending on the p53 mutation

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Bulut Bilişimin Eğitim Alanında Uygulanması

Bu çalışmada, Windows Azure platformu üzerinde, bulut bilişim temelli bir eğitim portalı geliştirilmiştir. Geliştirilen portal bir grup öğrenci ile uygulanarak eğitim sürecine katkıları incelenmiştir. Bulut bilişim eğitim alanında sunduğu olanaklar ve eğitim alanına uygulanabilirliği analiz edilmiştir. Bulut bilişim modelinin geleneksel yazılım modelinden farklı yönleri vurgulanarak, bulut bilişime geçişi gerekli kılan senaryolar yorumlanmıştır

The antimicrobial activity of ephedrine and admixture of ephedrine and propofol: an in vitro study

Introduction: Propofol and Ephedrine are commonly used during anesthesia maintenance, the former as a hypnotic agent and the later as a vasopressor. The addition of propofol to ephedrine or administration of ephedrine before propofol injection is useful for decreasing or preventing propofol related hemodynamic changes and vascular pain. This in vitro study evaluated the antibacterial effect on common hospital-acquired infection pathogens of ephedrine alone or combined with propofol. Material and method: The study was performed in two stages. In the first, the Minimum Inhibitory Concentration of propofol and ephedrine alone and combined was calculated for Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and a clinical isolate of Acinetobacter spp. at 0, 6, 12 and 24 h, using the microdilution method. In the second stage, the same drugs and combination were used to determine their effect on bacterial growth. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1/100 concentration. Colony numbers were measured as colony forming units.mL−1 at 0, 2, 4, 6, 8, 10 and 12th hours. Results: Ephedrine either alone or combined with propofol did not have an antimicrobial effect on Escherichia coli, Enterococcus faecium, or Pseudomonas aeruginosa and this was similar to propofol. However, ephedrine alone and combined with propofol was found to have an antimicrobial effect on Staphylococcus aureus and Acinetobacter species at 512 mcg.mL−1 concentration and significantly decreased bacterial growth rate. Conclusion: Ephedrine has an antimicrobial activity on Staphylococcus aureus and Acinetobacter species which were frequently encountered pathogens as a cause of nosocomial infections. Resumo: Introdução: Propofol e efedrina são fármacos comumente usados durante a manutenção da anestesia, o primeiro como agente hipnótico e o segundo como vasopressor. A adição de propofol à efedrina ou a administração de efedrina antes da injeção de propofol é útil para diminuir ou prevenir alterações hemodinâmicas e dor vascular relacionadas ao propofol. Este estudo in vitro avaliou o efeito antibacteriano de efedrina, isolada ou em combinação com propofol, em patógenos comuns implicados em infecção hospitalar. Material e método: O estudo foi realizado em duas etapas. Na primeira, a concentração inibitória mínima (CIM) de propofol e de efedrina isolada e em combinação foi calculada para Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa e um isolado clínico de Acinetobacter spp às 0, 6, 12 e 24 horas, usando o método de microdiluição. Na segunda etapa, o mesmo fármaco e sua combinação foram utilizados para determinar seus efeitos no crescimento bacteriano. As soluções bacterianas foram preparadas em soro fisiológico a 0,9% em 0,5 McFarland e diluídas a uma concentração de 1/100. Os números das colônias foram medidos como cfu.mL−1 às 0, 2, 4, 6, 8, 10 e 12 horas. Resultados: Efedrina isolada ou em combinação com propofol não apresentou efeito antimicrobiano sobre E. coli, E. faecium ou P. aeruginosa, um resultado semelhante ao de propofol. Porém, efedrina isolada e em combinação com propofol apresentou efeito antimicrobiano sobre Staphylococcus aureus e Acinetobacter spp, em concentração de 512 mcg.mL−1, e redução significativa da taxa de crescimento bacteriano. Conclusão: Efedrina tem atividade antimicrobiana em S. aureus e Acinetobacter spp, que são patógenos frequentemente identificados como causa de infecções nosocomiais. Keywords: Ephedrine, Propofol, Antimicrobial, Palavras-chave: Efedrina, Propofol, Antimicrobian

Erector Spinae Plane Block for Different Laparoscopic Abdominal Surgeries: Case Series

The ultrasound guided erector spinae plane (ESP) block is a recent block described for various surgeries for postoperative analgesia. ESP block has effect on both visceral and somatic pain; therefore, its use in laparoscopic cholecystectomy and other abdominal surgeries can be advantageous. We describe successful ESP block application in three different cases for postoperative pain. Two patient were operated on using endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy and one patient was operated on using laparoscopic cholecystectomy together with the inguinal hernia operation

The antimicrobial activity of ephedrine and admixture of ephedrine and propofol: an in vitro study

Abstract Introduction Propofol and Ephedrine are commonly used during anesthesia maintenance, the former as a hypnotic agent and the later as a vasopressor. The addition of propofol to ephedrine or administration of ephedrine before propofol injection is useful for decreasing or preventing propofol related hemodynamic changes and vascular pain. This in vitro study evaluated the antibacterial effect on common hospital-acquired infection pathogens of ephedrine alone or combined with propofol. Material and method The study was performed in two stages. In the first, the Minimum Inhibitory Concentration of propofol and ephedrine alone and combined was calculated for Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and a clinical isolate of Acinetobacter spp. at 0, 6, 12 and 24 h, using the microdilution method. In the second stage, the same drugs and combination were used to determine their effect on bacterial growth. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1/100 concentration. Colony numbers were measured as colony forming units.mL-1 at 0, 2, 4, 6, 8, 10 and 12th hours. Results Ephedrine either alone or combined with propofol did not have an antimicrobial effect on Escherichia coli, Enterococcus faecium, or Pseudomonas aeruginosa and this was similar to propofol. However, ephedrine alone and combined with propofol was found to have an antimicrobial effect on Staphylococcus aureus and Acinetobacter species at 512 mcg.mL-1 concentration and significantly decreased bacterial growth rate. Conclusion Ephedrine has an antimicrobial activity on Staphylococcus aureus and Acinetobacter species which were frequently encountered pathogens as a cause of nosocomial infections

Anti-Müllerian hormone and ovarian response in ıntrauterine ınsemination cycles: A prospective study

Amaç: Çalışmamızın amacı, intrauterin inseminasyon sikluslarında, over rezervini değerlendirmede antimüllerian hormon ile diğer rezerv belirteçlerini karşılaştırarak antimüllerian hormonun güvenilirliğinin araştırılmasıdır. Gereç ve Yöntem: Eylül 2009 ile Mayıs 2011 tarihleri arasında Ege Üniversitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum Kliniği İnfertilite Bölümü’ne başvuran ve intrauterin inseminasyon yapılan 80 hasta değerlendirilmiştir. Bu hastaların 9’unda polikistik over ve hipotalamohipofizer yetmezlik tanısı konulması üzerine çalışma grubuna dahil edilmediler ve çalışmaya dahil edilen 71 hasta klomifen sitrat ve gonadotropin kullanılan hastalar olarak iki gruba ayrıldı. Her iki grup, over yanıtına göre kendi arasında düşük, normal ve fazla over yanıtı olarak ayrılarak gruplar bazal AMH, LH, FSH, E2, PRL, yaş, antral follikül sayısı, gebelik açısından karşılaştırıldı. Bulgular: Klomifen sitrat ve gonadotropin verilen gruplar karşılaştırıldığında sadece infertilite süreleri arasında istatiksel fark saptandı (p<0,01). Düşük, normal, fazla over yanıtına göre AMH, FSH, LH, antral follikül sayısı, yaş, E2 değerleri karşılaştırıldığında istatiksel olarak anlamlılık saptanmamıştır. AMH’ın antral follikül sayısı (p<0,01) ve yaş (p<0,05) ile korele olduğu saptanmıştır. Klinik gebelik ile over yanıtı arasında istatiksel fark saptanmamıştır. Sonuç: Sonuç olarak, temel bulgu serum AMH konsantrasyonunun rFSH ve klomifen sitrat ile tedavi edilen ovulatuar IUI hastalarında over cevabını tahmin etmede anlamlı olmadığı ancak AMH’ın antral follikül sayısı ve yaş ile korele olduğudur.Objective: The purpose was to investigate the AMH level and other ovarian reserve markers in the different ovarian response groups. Material and Methods: 80 patients treated with intrauterine insemination were evaluated who were admitted to the Infertility Clinic, Department of Obstetrics and Gynecology of Ege University between September 2009 and May 2011. According to ovarian response each of the groups were divided as less, normal, more ovarian response subgroups and these subgroups were compared for basal AMH, LH, FSH, E2, PRL, age, number of antral follicles and pregnancy. Results: There was found only statistical difference between duration of infertility when Clomiphene citrate and gonadotropin-given groups were compared(p <0.01). According to low, normal and more ovarian response, there was no statistically significance when compared AMH, FSH, LH, antral folliclecount, age, E2 values. The AMH was correlated with antral follicle count (p <0.01) and the age (p <0.05). Conclusion: The serum AMH concentration was only slightly - and not statistically significant different for the IUI patients with a low, a normal or a high ovarian respons

YouTube as an information source of spinal anesthesia, epidural anesthesia and combined spinal and epidural anesthesia

Introduction: Social media as YouTube have become a part of daily life and many studies evaluated health-related YouTube videos. Our aim was to evaluate videos available on YouTube for the conformity to textbook information and their sufficiency as a source for patient information. Material and method: A search of the YouTube website was performed using the keywords “spinal anesthesia, epidural anesthesia, combined spinal epidural anesthesia”. Firstly, 180 videos were evaluated and the characteristics of the video were noted, and the features of the video too were noted if the video was regarding neuraxial anesthesia. Questionnaire 1 (Q1) evaluating the video quality relating to neuraxial anesthesia was designed using a textbook as reference and questionnaire 2 (Q2) was designed for evaluating patient information. Results: After exclusions, 40 videos were included in the study. There was no difference in Q1 or Q2 scores when videos were grouped into 4 quarters according to their appearance order, time since upload or views to length rate (p > 0.05). There was no statistical difference between Q1 or Q2 scores for spinal, epidural or combined videos (p > 0.05). Videos prepared by a healthcare institute have a higher score in both Questionnaires 1 and 2 (10.87 ± 4.28 vs. 5.84 ± 2.90, p = 0.044 and 3.89 ± 5.43 vs. 1.19 ± 3.35, p = 0.01 respectively). Conclusion: Videos prepared by institutes, societies, etc. were of higher educational value, but were still very lacking. Videos should be prepared in adherence to available and up-to-date guidelines taking into consideration appropriate step by step explanation of each procedure, patient safety and frequently asked questions. Resumo: Introdução: As mídias sociais como o YouTube tornaram-se uma parte do cotidiano e muitos estudos avaliaram vídeos do YouTube relacionados à saúde. Nosso objetivo foi avaliar os vídeos disponíveis no YouTube para identificar a existência de conformidade com as informações em livros didáticos e sua suficiência como fonte de informação para o paciente. Material e método: Uma pesquisa no site YouTube foi realizada usando as palavras-chave spinal anesthesia, epidural anesthesia, combined spinal-epidural anesthesia (raquianestesia, anestesia peridural, anestesia combinada raqui peridural). Em primeiro lugar, avaliamos 180 vídeos e observando suas características e se eram referentes à anestesia neuraxial. O questionário de avaliação da qualidade do vídeo (Q1) relativa à anestesia neuraxial foi criado usando um livro didático como referência e o questionário 2 (Q2) foi criado para avaliar as informações ao paciente. Resultados: Após exclusões, 40 vídeos foram incluídos no estudo. Não houve diferença nos escores de Q1 ou Q2 quando os vídeos foram agrupados em quatro categorias de acordo com a ordem de aparecimento, tempo de upload ou taxa de tempo de visualização (p > 0,05). Não houve diferença estatística entre os escores de Q1 ou Q2 para os vídeos raquianestesia, peridural ou combinada (p > 0,05). Os vídeos preparados por um instituto de saúde obtiveram escores mais elevados em ambos Q1 e Q2 (10,87 ± 4,28 vs. 5,84 ± 2,90, p = 0,044 e 3,89 ± 5,43 vs. 1,19 ± 3,35, p = 0,01, respectivamente). Conclusão: Os vídeos elaborados por institutos, sociedades etc. apresentaram um valor educativo maior, mas ainda muito incompleto. Os vídeos devem ser preparados em conformidade com as diretrizes atualizadas e disponíveis, com explicações adequadas e detalhadas sobre cada procedimento, segurança do paciente e perguntas mais frequentes. Keywords: Youtube, Anesthesia, Spinal, Epidural, Palavras-chave: YouTube, Anestesia, Raquidiana, Peridura

[YouTube as an informational source for brachial plexus blocks: evaluation of content and educational value].

YouTube, the most popular video-sharing website, contains a significant number of medical videos including brachial plexus nerve blocks. Despite the widespread use of this platform as a medical information source, there is no regulation for the quality or content of the videos. The goals of this study are to evaluate the content of material on YouTube relevant to performance of brachial plexus nerve blocks and its quality as a visual digital information source

Anti-Müllerian hormone and ovarian response in ıntrauterine ınsemination cycles: A prospective study

Amaç: Çalışmamızın amacı, intrauterin inseminasyon sikluslarında, over rezervini değerlendirmede antimüllerian hormon ile diğer rezerv belirteçlerini karşılaştırarak antimüllerian hormonun güvenilirliğinin araştırılmasıdır. Gereç ve Yöntem: Eylül 2009 ile Mayıs 2011 tarihleri arasında Ege Üniversitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum Kliniği İnfertilite Bölümü’ne başvuran ve intrauterin inseminasyon yapılan 80 hasta değerlendirilmiştir. Bu hastaların 9’unda polikistik over ve hipotalamohipofizer yetmezlik tanısı konulması üzerine çalışma grubuna dahil edilmediler ve çalışmaya dahil edilen 71 hasta klomifen sitrat ve gonadotropin kullanılan hastalar olarak iki gruba ayrıldı. Her iki grup, over yanıtına göre kendi arasında düşük, normal ve fazla over yanıtı olarak ayrılarak gruplar bazal AMH, LH, FSH, E2, PRL, yaş, antral follikül sayısı, gebelik açısından karşılaştırıldı. Bulgular: Klomifen sitrat ve gonadotropin verilen gruplar karşılaştırıldığında sadece infertilite süreleri arasında istatiksel fark saptandı (p<0,01). Düşük, normal, fazla over yanıtına göre AMH, FSH, LH, antral follikül sayısı, yaş, E2 değerleri karşılaştırıldığında istatiksel olarak anlamlılık saptanmamıştır. AMH’ın antral follikül sayısı (p<0,01) ve yaş (p<0,05) ile korele olduğu saptanmıştır. Klinik gebelik ile over yanıtı arasında istatiksel fark saptanmamıştır. Sonuç: Sonuç olarak, temel bulgu serum AMH konsantrasyonunun rFSH ve klomifen sitrat ile tedavi edilen ovulatuar IUI hastalarında over cevabını tahmin etmede anlamlı olmadığı ancak AMH’ın antral follikül sayısı ve yaş ile korele olduğudur.Objective: The purpose was to investigate the AMH level and other ovarian reserve markers in the different ovarian response groups. Material and Methods: 80 patients treated with intrauterine insemination were evaluated who were admitted to the Infertility Clinic, Department of Obstetrics and Gynecology of Ege University between September 2009 and May 2011. According to ovarian response each of the groups were divided as less, normal, more ovarian response subgroups and these subgroups were compared for basal AMH, LH, FSH, E2, PRL, age, number of antral follicles and pregnancy. Results: There was found only statistical difference between duration of infertility when Clomiphene citrate and gonadotropin-given groups were compared(p <0.01). According to low, normal and more ovarian response, there was no statistically significance when compared AMH, FSH, LH, antral folliclecount, age, E2 values. The AMH was correlated with antral follicle count (p <0.01) and the age (p <0.05). Conclusion: The serum AMH concentration was only slightly - and not statistically significant different for the IUI patients with a low, a normal or a high ovarian respons