Concurrency in leukocyte vascular recognition: developing the tools for a predictive computer model

Leukocyte recruitment has a crucial role in inflammation and immunity. An interplay between adhesion molecules and pro-adhesive agonists generates a complex molecular network controlling tissue-specific and inflammation-dependent leukocyte vascular recognition. Recent findings highlight the importance of quantitative parameters in controlling the specificity of leukocyte vascular recognition. Introduction of quantitative parameters demonstrates the non-linear behavior of the process and suggests the necessity for a revision of the traditional model. We propose a formalization of the original multi-step model of leukocyte vascular recognition by introducing the notion of concurrency that explains how the quantitative variation of pro-adhesive parameters might control the specificity and the sensitivity of this process. Moreover, we discuss how concurrency, by integrating quantitative parameters, constitutes a central concept for the implementation of a predictive computer modeling of leukocyte vascular recognition

Health Care Information Technology: Securing the Electronic Health Record with Biometric Technology

The principal focus of this paper is to examine the integration of biometric technology into healthcare’s information technology systems. Biometric technology, a rapidly evolving mechanism, analyzes specific anatomical and physiological features of an individual for identity verification (Perrin, 2002). Moreover, as the federal government has mandated all health records to be electronic in 2014, the implementation of biometrics has become a prevalent means of security. In an effort to adhere to the patient privacy laws authorized by the Health Insurance Portability and Accountability Act (HIPAA), biometric recognition is currently used to restrict access to verified health care providers and detect fraudulent account access. This paper considers the advantages, disadvantages, and ethical consequences of utilizing biometric technology to secure the electronic health record in regards to cost, usability, accessibility, and accuracy. In addition to evaluating the primary application, the essay acknowledges the potential use of biometric technology to identify patients by vasculature scanning in the future

The effects of Bordetella pertussis on dendritic cell imprinting of CD4+ T cells

Bordetella pertussis is an aerobic gram-negative bacterial pathogen that causes the human respiratory disease whooping cough. Despite widespread vaccination, whooping cough is reemerging due to decreased vaccine efficacy. One of the hallmarks of infection is lymphocytosis, which is induced by the pertussis toxin. Lymphocytes such as CD4+ T cells navigate to infected tissues through surface-trafficking molecules, which are imprinted during their interaction with tissue-associated dendritic cells. We hypothesized that the pertussis toxin affects the imprinting process resulting in altered expression of trafficking molecules on CD4+ T cells. We tested this hypothesis using a mouse model of infection. Imprinting levels on CD4+ T cells were compared to Bordetella parapertussis, a related strain that lacks pertussis toxin. Our results indicated that 5 days post-infection, the percentage of lung dendritic cells increased and adopted a mature phenotype (displaying an increased capability to migrate and present antigen to T cells) in response to B. pertussis infection, and there was an overall downregulation of trafficking molecules on CD4+ T cells. However, 25 days post-infection with B. pertussis, dendritic cells continued to express elevated levels of MHC class II, and the expression of trafficking markers on CD4+ T cells also increased compared to uninfected controls. These results enable identification of molecules that are specific for lymphocyte trafficking to the respiratory airways and contribute to knowledge useful in the development of better vaccines

토끼 VX2 간종양 모델을 이용한 전임상 연구

학위논문(박사) -- 서울대학교대학원 : 의과대학 의학과, 2021.8. 정진욱.Introduction: Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. The aim of this study was to prove the feasibility of albumin-doxorubicin nanoparticle conjugated microbubble (ADMB) for enhancing therapeutic efficiency by sonoporation under exposure to ultrasound, and to develop a novel drug delivery system composed of doxorubicin-loaded albumin nanoparticles-conjugated microbubble complex in iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) to overcome these limitations and to evaluate safety and therapeutic efficacy of ultrasound-triggered TACE using this formulation. Materials and methods: This study was comprised of two parts; the first part was for fabrication and evaluation of in-vitro characteristics of ADMB, including size distribution, drug release profile, and echogenicity. Therapeutic efficacy was assessed using rabbit VX2 tumor model. The second part was for development and in-vivo validation of DOX-NPs-MB complex in iodized oil emulsion as a new ultrasound-triggered TACE formulation. Results: ADMB demonstrated a size distribution of 2.33 ± 1.34 µm and a doxorubicin loading efficiency of 82.7%. The echogenicity of ADMBs was sufficiently generated in the 2–9 MHz frequency range and cavitation depended on the strength of the irradiating ultrasound. DOX-NPs-MB constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In the in vivo study, ultrasound-triggered TACE using DOX-NPs-MB complex in Lipiodol formulation (US+) showed a lower viable tumor portion than the conventional TACE formulation, and effectively killed cancer cells in the peripheral region of the tumor. Liver toxicity was comparable to that of conventional therapies. Conclusion: In summary, by introducing a doxorubicin-loaded microbubble in the TACE formulation, it was possible to improve both drug delivery to the tumor with real-time monitoring, and therapeutic efficacy of TACE. This enhanced TACE formulation may provide a new means of treating liver cancer.서론: 경동맥화학색전술 (Transarterial chemoembolization; TACE)는 간암의 국소 치료에서 중요한 위치를 차지하고 있는 치료법이다. 그러나 고식적인 TACE는 주입한 에멀젼이 불안정하여 혈액 내에서 빠르게 분리되면서 국소 약물 전달 효과는 떨어지고 전신 부작용이 생기는 문제점이 있다. 본 연구는, 이와 같은 TACE의 한계를 극복하기 위한 초음파 감응형 항암제 함유 알부민 나노입자-마이크로버블 복합체와, 이 복합체와 요오드화 기름과의 새로운 에멀젼을 개발하여 약물전달능 및 종양살상능을 향상시키는 새로운 초음파 감응형 간동맥화학색전술용 에멀젼을 개발하는 것이다. 방법: 이 연구는 크게 2 단계로 구분되어 있다. 먼저 항암제 함유 나노입자-마이크로버블 복합체 (Albumin nanoparticle-Doxorubicin conjugated Microbubble; ADMB) 를 제작하고 물리화학적 특성 을 분석하였다. In-vivo study를 위하여 토끼 VX2 간종양 모델을 이용하였다. 최종적으로 개발된 ADMB와 iodized oil과의 에멀젼을 이용하여 in-vitro characteristics 및in-vivo therapeutic efficacy 와 safety를 검증하였다. 결과: ADMB는 약 2.33 ± 1.34 µm 의 크기를 가지며 doxorubicin loading efficiency는 82.7%였다. ADMB는 2–9 MHz 주파수 범위에서 가시적인 초음파 조영능을 보였으며 방사하는 초음파 세기에 따라 cavitation 효과를 보였다. 토끼 간종양 모델을 이용한 실험에서 ADMB군은 치료를 하지 않은 대조군에 비해 약 5배의 종양 성장 억제 효과를 보였다. DOX-NPs-MB 에멀젼 역시 ADMB와 유사한 정도의 초음파 조영능을 보였고 in-vivo 실험에서 새로 개발된 DOX-NPs-MB 에멀젼을 외부 초음파와 감응시키면서 종양에 주입하였을 때, 기존 에멀젼보다 유의하게 높은 종양 살상능을 보였고 간독성에는 두 군간 차이가 없었다. 결론: 새로 개발된 외부 초음파 감응형 DOX-NPs-MB 에멀젼은 기존의 고식적인 에멀젼보다 약물 전달능, 종양 살상능이 우수하였으며 초음파로 실시간 약물 전달 모니터링이 가능하였다. 이 새 에멀젼은TACE에서 간암 치료 효과를 높일 수 있는 새로운 수단이 될 것으로 기대된다.Abstract 3 Introduction 8 Materials and Methods 10 Results 23 Discussion 47 Conclusion 54 References 57박

Imaging of melanoma: usefulness of ultrasonography before and after contrast injection for diagnosis and early evaluation of treatment

High-frequency ultrasound (8–14 MHz) is routinely used to display cutaneous melanomas. Maximum thickness measurement (Breslow index) has been shown to be well correlated to histologic findings for lesions of more than 0.75 mm. Some morphological criteria (strong delineation, hypoechoic texture, homogeneity) have been reported to help differentiate between malignant and benign pigmented blue lesions, but remain insufficient. Vascular ultrasound analysis using Doppler mode provides additional information and showed good specificity for malignancy (90%–100%), but variable sensitivity (34%–100%). Recent advances in ultrasound imaging allow functional evaluation. Likewise, dynamic contrast-enhanced ultrasound using contrast medium injection and specific perfusion and quantification software showed promising results in clinical and preclinical trials for early prediction of tumor response to target treatments

Photoacoustic topography through an ergodic relay for functional imaging and biometric application in vivo

Significance: Photoacoustic (PA) tomography has demonstrated versatile biomedical applications. However, an array-based PA computed tomography (PACT) system is complex and expensive, whereas a single-element detector-based scanning PA system is too slow to detect some fast biological dynamics in vivo. New PA imaging methods are sought after. Aim: To overcome these limitations, we developed photoacoustic topography through an ergodic relay (PATER), a novel high-speed imaging system with a single-element detector. Approach: PATER images widefield PA signals encoded by the acoustic ergodic relay with a single-laser shot. Results: We applied PATER in vivo to monitor changes in oxygen saturation in a mouse brain and also to demonstrate high-speed matching of vascular patterns for biometric authentication. Conclusions: PATER has achieved a high-speed temporal resolution over a large field of view. Our results suggest that PATER is a promising and economical alternative to PACT for fast imaging

Photoacoustic topography through an ergodic relay for functional imaging and biometric application in vivo

Significance: Photoacoustic (PA) tomography has demonstrated versatile biomedical applications. However, an array-based PA computed tomography (PACT) system is complex and expensive, whereas a single-element detector-based scanning PA system is too slow to detect some fast biological dynamics in vivo. New PA imaging methods are sought after. Aim: To overcome these limitations, we developed photoacoustic topography through an ergodic relay (PATER), a novel high-speed imaging system with a single-element detector. Approach: PATER images widefield PA signals encoded by the acoustic ergodic relay with a single-laser shot. Results: We applied PATER in vivo to monitor changes in oxygen saturation in a mouse brain and also to demonstrate high-speed matching of vascular patterns for biometric authentication. Conclusions: PATER has achieved a high-speed temporal resolution over a large field of view. Our results suggest that PATER is a promising and economical alternative to PACT for fast imaging

Determination and recognition of the net of blood vessels of the finger

Recognition of blood vessels on the fingers is considered one of the most promising biometric technologies for identity authentication. However, the percentage of finger tissue (eg, bones, muscles, ligaments, water, fat, etc.) varies from person to person. Typically, this results in poor image quality of the finger vessels, which reduces the performance of the finger vascular recognition (FVRS) systems. This paper analyzes the internal factors of finger tissue that cause poor image quality of finger vessels and proposes a method to normalize intensity variation using a single-level retinex based on a controlled filter (GFSSR) to improve finger vessel imaging and recognition accuracy. This will allow the use of this technique for integration into existing medical systems and reduce the burden on medical staff and improve the quality and timeliness of patient care