234 research outputs found

    The ins and outs of open-angle Glaucoma:drugs, diet, and defecation

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    Glaucoma is the leading cause of irreversible blindness and second leading cause of blindness. The primary aim of this thesis is to provide insight into the role of systemic effectsin the pathophysiology of OAG.<br/

    Proton and alpha radiation-induced mutational profiles in human cells

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    Ionizing radiation is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of radiation. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of galactic cosmic radiation, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the human blood, breast and lung to fractionated proton and alpha particle (helium nuclei) beams at doses sufficient to considerably affect cell viability. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were modest changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may be cell-type and/or genetic background specific. Overall, the mutational effects of repeated exposures to proton and alpha radiation on human cells in culture appear subtle, however further work is warranted to understand effects of long-term exposures on various human tissues.© 2023. The Author(s)

    The fungal skin microbiota of healty and dermatoses-affected areas in HIV-positive and HIV-negative children

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    The purpose of the study is to investigate the Candida, Malassezia, Saccharomyces, and Debaryomyces species composition in dermatoses-affected and healthy skin samples from HIV-positive and HIV-negative children.Цель исследования – изучить видовой состав грибов рода Candida, Malassezia, Saccharomyces и Debaryomyces в соскобах с участков кожи, пораженных дерматозом, и неизмененных у ВИЧ-положительных и ВИЧ-отрицательных детей

    개의 원발성 녹내장 발생 현황과 안방수 Proteomic 분석에 대한 연구

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    학위논문(박사) -- 서울대학교대학원 : 수의과대학 수의학과, 2023. 2. 서강문.본 연구에서는 개의 원발성 녹내장 발생현황과 원발성 녹내장의 병인을 밝히기 위해 원발성 녹내장 개의 품종, 나이, 성별을 조사하고 안방수의 단백체를 확인하고 분석하였다. 제 1 장에서는 원발성 녹내장이 있는 개의 품종, 나이, 성별의 발생 현황을 한국에서의 이전 보고와 비교하였다. 2011 년 1 월부터 2020 년 12 월 까지 서울대학교 동물병원에 내원한 원발성 녹내장으로 진단된 개들의 품종, 나이, 성별 등의 의료 기록을 조사하였다. 모든 환자들에서 안과 정밀검사가 시행되었다. 분석은 원발성 녹내장의 평균 발생율과 가장 가까운 진돗개의 발생률을 기준으로 이항 로지스틱 회귀 분석을 통하여 분석되었다. 서울대학교 동물병원에 내원한 14,587 마리의 개 중에 107 마리가 원발성 녹내장으로 진단되었다. 원발성 녹내장은 아메리칸 코카 스페니얼, 시츄, 말티즈, 포메라니언, 진도견, 혼합견, 페키니즈, 토이 푸들, 사모이드, 시바이누, 미니핀, 보스턴 테리어, 라브라도 리트리버, 요크셔 테리어를 포함한 14 품종에서 발생하였다. 원발성 녹내장의 평균 발생 나이는 7.8 ±2.3 세 였고, 53 마리의 중성화 암컷, 11 마리의 암컷, 38 마리의 중성화 수컷,5 마리의 수컷에서 관찰되었다. 중성화와 관계없는 암컷, 수컷의 비율은 1.5:1 이었다. 본 연구에서 원발성 녹내장은 다른 품종보다 아메리칸 코카 스페니얼에서 유의적으로 높게 나타났으며, 시츄에서도 높게 확인되었으며, 7, 8 세에서 각각 높은 발생률을 보였다. 따라서, 두 품종은 7 세가 되면 원발성 녹내장 발생을 주의 깊게 관찰해야 할 것으로 판단된다. 제 2 장에서는 원발성 폐쇄우각 녹내장이 있는 개에서 안방수의 단백체를 분석하고 관련된 단백체의 변화를 확인하였다. 여섯 마리의 폐쇄우각 녹내장이 있는 아메리칸 코커 스페니얼과 안과 질환이 없는 여섯 마리의 아메리칸 코카 스페니얼의 안방수를 채취하였다. 비친코닌산(BCA) 분석으로 안방수의 총단백질 농도를 측정하였다. 안방수 단백질은 액체 크로마토그래피 질량 분석법 (LC-MS/MS)으로 분석하고 유전자 분석은 ClueGO 기법을 사용하여 수행되었다. 단백질 농도는 폐쇄우각 녹내장 그룹에서 (10.49 ± 17.98 µg/µl) 대조군 (0.45 ± 0.11 µg/µl) 보다 유의적으로 높았다 (p < 0.05). 안방수에서 총 758 개의 단백질이 확인되었다. 여러 단백질들이 폐쇄우각 녹내장 그룹에서 유의적으로 증가 (n=69) 하거나, 감소 (n=252) 하였다. 상위 5 개 단백질은 인산단백질 1 (SPP1), 펩티도글리칸 인식단백질 2 (PGLYRP2), 티로신 3-모노옥시게나아제 (YWHAE), 말타아제글루코아밀라아제 (MGAM), 비멘틴 (VIM) 이었다. 단백체 데이터를 이용한 유전자 분석을 통하여 폐쇄우각 녹내장의 마지막 단계에서 볼 수 있는 염증과 관련된 안방수 단백질들과 경로들이 유의적으로 높게 나타났음을 알 수 있었다. 폐쇄우각 녹내장 환자의 안방수 단백체 분석은 폐쇄우각 녹내장의 병인론에 대한 중요한 정보를 제공할 수 있을 것으로 생각된다. 결론적으로, 아메리칸 코커 스페니엘과 시츄는 7 세 때 원발성 녹내장의 발생을 고려해야 하며, 원발성 녹내장 환자의 안방수 분석으로 원발성 녹내장 진단에 필요한 잠재적인 바이오마커가 될 수 있는 단백체들을 확인할 수 있었다This study investigated the prevalence of breed, age, and sex of canine primary glaucoma patients, and analyzed the aqueous humor (AH) of canines with primary angle-closure glaucoma (PACG). In chapter 1, the prevalence of canine primary glaucoma by breed, age, and sex was compared with previous reports in Korea. We included the medical records of dogs diagnosed with primary glaucoma who visited the veterinary medical teaching hospital of Seoul National University (SNU) from January 2011 to December 2020 and investigated their breed, age, and sex. All the patients underwent a full ophthalmic examination. We analyzed the results using a binary logistic regression analysis based on the Jindo dog, which was close to the mean value of the primary glaucoma incidence rate. Of the 14,587 dogs treated at the veterinary medical teaching hospital of SNU, 107 (0.73%) were diagnosed with primary glaucoma. Glaucoma occurred in 14 breeds, including American Cocker Spaniel, Shih Tzu, Maltese, Pomeranian, Jindo dog, Mixed Breed, Pekinese, Toy Poodle, Samoyed, Shiba Inu, Miniature Pinscher, Boston Terrier, Labrador retriever, and Yorkshire Terrier. The mean age of onset of primary glaucoma was 7.8 ± 2.3 years old. Primary glaucoma was observed in 53 spayed females, 11 females, 38 castrated males, and 5 males. Regardless of neutralization, the ratio of females to males was 1.5:1. This study showed that primary glaucoma was significantly higher in American Cocker Spaniels and higher in Shih Tzus than other breeds in Korea; they had the highest incidence of primary glaucoma at 7 and 8 years of age, respectively. Therefore, the two breeds should be carefully monitored for the occurrence of primary glaucoma when they approach 7 years of age. In chapter 2, proteomic profiles of the aqueous humor (AH) of canines with primary angle-closure glaucoma (PACG) was analyzed and associated protein alterations was identified. Six American Cocker Spaniels with PACG and six American Cocker Spaniels without ocular disease. Total AH protein concentration was determined by the bicinchoninic acid (BCA) assay. AH protein samples were quantified by liquid chromatography-mass spectrometry (LC-MS/MS) and the Gene Ontology (GO) enrichment analysis was performed using ClueGO. The AH protein concentration in the PACG group (10.49 ± 17.98 µg/µl) was significantly higher than that of the control group (0.45 ± 0.11 µg/µl; p < 0.05). A total of 758 proteins were identified in the AH. Several proteins both significantly increased (n=69) and decreased (n=252) in the PACG group compared to those in the control group. GO enrichment analysis showed that the response to wounding, negative regulation of endopeptidase activity and cell growth pathways were the most enriched terms in the PACG group compared to the control group. The top 5 proteins that were significantly increased in the AH of the PACG group were secreted phosphoprotein 1 (SPP1), peptidoglycan recognition proteins 2 (PGLYRP2), tyrosine 3-monooxygenase (YWHAE), maltase-glucoamylase (MGAM), and vimentin (VIM). Gene Ontology enrichment analysis using the proteomic data showed that proteins and pathways related to inflammation were significantly upregulated in the various stage of PACG. Proteomic analysis of the AH from the PACG may provide valuable insights into PACG pathogenesis. In conclusion, Shih Tzu and Cocker Spaniel should be concerned about primary glaucoma at the age of seven and the aqueous humor analysis of primary glaucoma patients, and identified proteins which are potential biomarkers for assessing increased risk.GENERAL INTRODUCTION 1 CHAPTER I A Retrospective Study of Canine Primary Glaucoma (2011-020) 5 1.1 ABSTRACT 6 1.2I NTRODUCTION 7 1.3 MATERIALS AND METHODS 9 1.4 RESULTS 11 1.5 DISCUSSION 15 1.6 CONCLUSION 19 CHAPTER II Proteomic analysis of aqueous humor in canine primary angle-closure glaucoma in American Cocker Spaniel dogs 20 2.1 ABSTRACT 21 2.2 INTRODUCTION 23 2.3 MATERIALS AND METHODS 2.3.1. Animals studied and preparation 26 2.3.2. Aqueous humor collection 27 2.3.3. Total protein quantification 27 2.3.4. Sample preparation and labeling 28 2.3.5. Liquid chromatography-mass spectrometry analysis 28 2.3.6. Protein identification 29 2.3.7. Data analysis for protein profiling 30 2.3.8. Peptidoglycan recognition proteins 2 detection by Western blot 30 2.3.9.. Statistical analysis 31 2.4 RESULTS 32 2.4.1. Ophthalmic examination of primary angle-closure glaucoma group 32 2.4.2. Aqueous humor protein concentrations in the PACG and control 38 2.4.3. Protein identification 4 0 2.4.4. Western blot analysis of peptidoglycan recognition proteins 2 47 2.5.DISCUSS ION 4 8 2.6 CONCLUSION 55 GENERAL CONCLUSIONS 5 6 REFERENCES 57 ABSTRACT IN KOREAN 67 ACKNOWLEDGEMENTS 70박

    Evaluation of randomized controlled trials: a primer and tutorial for mental health researchers

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    Background Considered one of the highest levels of evidence, results of randomized controlled trials (RCTs) remain an essential building block in mental health research. They are frequently used to confirm that an intervention “works” and to guide treatment decisions. Given their importance in the field, it is concerning that the quality of many RCT evaluations in mental health research remains poor. Common errors range from inadequate missing data handling and inappropriate analyses (e.g., baseline randomization tests or analyses of within-group changes) to unduly interpretations of trial results and insufficient reporting. These deficiencies pose a threat to the robustness of mental health research and its impact on patient care. Many of these issues may be avoided in the future if mental health researchers are provided with a better understanding of what constitutes a high-quality RCT evaluation. Methods In this primer article, we give an introduction to core concepts and caveats of clinical trial evaluations in mental health research. We also show how to implement current best practices using open-source statistical software. Results Drawing on Rubin’s potential outcome framework, we describe that RCTs put us in a privileged position to study causality by ensuring that the potential outcomes of the randomized groups become exchangeable. We discuss how missing data can threaten the validity of our results if dropouts systematically differ from non-dropouts, introduce trial estimands as a way to co-align analyses with the goals of the evaluation, and explain how to set up an appropriate analysis model to test the treatment effect at one or several assessment points. A novice-friendly tutorial is provided alongside this primer. It lays out concepts in greater detail and showcases how to implement techniques using the statistical software R, based on a real-world RCT dataset. Discussion Many problems of RCTs already arise at the design stage, and we examine some avoidable and unavoidable “weak spots” of this design in mental health research. For instance, we discuss how lack of prospective registration can give way to issues like outcome switching and selective reporting, how allegiance biases can inflate effect estimates, review recommendations and challenges in blinding patients in mental health RCTs, and describe problems arising from underpowered trials. Lastly, we discuss why not all randomized trials necessarily have a limited external validity and examine how RCTs relate to ongoing efforts to personalize mental health care

    Nanosistemas de administración oftálmica para el tratamiento de patologías crónicas e inflamatorias

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    Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 14-07-2022Chronic ocular diseases that involve inflammatory conditions affects both the anterior and posterior segments of the eye, which in many cases lack of effective and well tolerated treatments at the same time. These types of pathologies can be subdivided into two welldifferentiated groups: those induced by inflammatory processes that end up developing a vicious cycle, such as uveitis or conjunctivitis, and those generated by pathophysiological transformations, or modifications that evolve towards inflammatory and degenerative processes. This last instance would be the case of prevalent pathologies such as dry eye disease (DED) and glaucoma. In DED, changes on the ocular surface occur such as tear evaporation, change in the lipid or aqueous profile of the precorneal tear film among others. Meanwhile, in glaucoma a damage in the nervous fibers of the retina is produced associated in most cases to an IOP increment. In both cases a chronic inflammation is induced giving rise rise to chronic and degenerative processes of both the anterior segment (fibrosis, abrasion, corneal ulcerations, and vision loss) and the posterior segment of the eye (neuroinflammation, excitotoxicity and retinal neurodegeneration). In fact, there is growing evidence about the relation between neurodegenerative diaseases and inflammatory events...Las enfermedades oculares crónicas, que cursan con inflamación, afectan tanto al segmento anterior como al posterior y, en muchas ocasiones carecen de tratamientos quesean efectivos y que al mismo tiempo resulten bien tolerados. Este tipo de patologías se pueden dividir en dos categorías bien diferenciadas: aquellas inducidas por eventos inflamatorios que acaban generando un círculo vicioso, como la uveítis o la conjuntivitis, y las generadas por transformaciones o modificaciones fisiopatológicas que evolucionan hacia procesos inflamatorios y degenerativos. Esta última categoría sería el caso de patologías prevalentes como la enfermedad de ojo seco (EOS) y el glaucoma. En la EOS se producen, entre otros procesos, evaporación de la lágrima y/o alteraciones en el perfil lipídico o acuoso de la película precorneal. En el glaucoma se produce un daño en la capa de fibras nerviosas de la retina que se asocia, en la mayoría de los casos, a un aumento dela presión intraocular (PIO). En ambos casos se genera gradualmente una inflamación crónica, dando lugar a procesos degenerativos tanto del segmento anterior (fibrosis, abrasión y ulceraciones corneales) como posterior (neuroinflamación, excitotoxicidad y otros procesos neurodegenerativos de la retina). De hecho, cada vez hay más evidencia de que las enfermedades neurodegenerativas se asocian a eventos inflamatorios...Fac. de FarmaciaTRUEunpu

    Modelling and Uncertainty Quantification application to SA simulation codes in advanced SMR

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    In the framework of a global transition to a low-carbon energy mix, the interest in advanced nuclear Small Modular Reactors (SMRs) has been growing at the international level. Due to the high level of maturity reached by Severe Accident Codes for currently operating rectors, their applicability to advanced SMRs is starting to be studied. Within the present work of thesis and in the framework of a collaboration between ENEA, UNIBO and IRSN, an ASTEC code model of a generic IRIS reactor has been developed. The simulation of a DBA sequence involving the operation of all the passive safety systems of the generic IRIS has been carried out to investigate the code model capability in the prediction of the thermal-hydraulics characterizing an integral SMR adopting a passive mitigation strategy. The following simulation of 4 BDBAs sequences explores the applicability of Severe Accident Codes to advance SMRs in beyond-design and core-degradation conditions. The uncertainty affecting a code simulation can be estimated by using the method of Input Uncertainty Propagation, whose application has been realized through the RAVEN-ASTEC coupling and implementation on an HPC platform. This probabilistic methodology has been employed in a study of the uncertainty affecting the passive safety system operation in the DBA simulation of ASTEC, providing a further characterization of the thermal-hydraulics of this sequence. The application of the Uncertainty Quantification method to early core-melt phenomena has been investigated in the framework of a BEPU analysis of the ASTEC simulation of the QUENCH test-6 experiment. A possible solution to the encountered challenges has been proposed through the application of a Limit Surface search algorithm
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