Evaluation of lymphatic vessel dilatations by anterior segment swept-source optical coherence tomography: Case report

Background: Conjunctival lymphangiectasia is a rare condition presumably caused by the obstruction of lymphatic channels or by an abnormal connection between conjunctival lymphatic and blood vessels. Diagnosis is based on clinical appearance and histology. We report a case of conjunctival lymphangiectasia in which anterior segment optical coherence tomography (OCT) was used to assist the diagnosis and the planning of the biopsy location. Case presentation: A 31-year-old woman was referred with repeated episodes of conjunctival "hemorrhages" and chemosis with extended recovery periods over the last months. Other symptoms were dryness, redness, burning sensation and itching. Photo documentation, anterior segment OCT, ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed. MRI revealed dilated atypical Virchow-Robin space (VRS). Conjunctival biopsy was taken and the location of the biopsy was selected based on OCT findings. Based on the clinical appearance we suspected the case to be conjunctival lymphangiectasia or lymphangioma. Histology and immunhistochemistry confirmed the diagnosis of conjunctival lymphangiectasia. Conclusions: Anterior segment OCT is a non-invasive tool, useful in the evaluation of conjunctival lesions and planning surgery. © 2017 The Author(s)

Computational model of blood flow in the aorto-coronary bypass graft

BACKGROUND: Coronary artery bypass grafting surgery is an effective treatment modality for patients with severe coronary artery disease. The conduits used during the surgery include both the arterial and venous conduits. Long- term graft patency rate for the internal mammary arterial graft is superior, but the same is not true for the saphenous vein grafts. At 10 years, more than 50% of the vein grafts would have occluded and many of them are diseased. Why do the saphenous vein grafts fail the test of time? Many causes have been proposed for saphenous graft failure. Some are non-modifiable and the rest are modifiable. Non-modifiable causes include different histological structure of the vein compared to artery, size disparity between coronary artery and saphenous vein. However, researches are more interested in the modifiable causes, such as graft flow dynamics and wall shear stress distribution at the anastomotic sites. Formation of intimal hyperplasia at the anastomotic junction has been implicated as the root cause of long- term graft failure. Many researchers have analyzed the complex flow patterns in the distal sapheno-coronary anastomotic region, using various simulated model in an attempt to explain the site of preferential intimal hyperplasia based on the flow disturbances and differential wall stress distribution. In this paper, the geometrical bypass models (aorto-left coronary bypass graft model and aorto-right coronary bypass graft model) are based on real-life situations. In our models, the dimensions of the aorta, saphenous vein and the coronary artery simulate the actual dimensions at surgery. Both the proximal and distal anastomoses are considered at the same time, and we also take into the consideration the cross-sectional shape change of the venous conduit from circular to elliptical. Contrary to previous works, we have carried out computational fluid dynamics (CFD) study in the entire aorta-graft-perfused artery domain. The results reported here focus on (i) the complex flow patterns both at the proximal and distal anastomotic sites, and (ii) the wall shear stress distribution, which is an important factor that contributes to graft patency. METHODS: The three-dimensional coronary bypass models of the aorto-right coronary bypass and the aorto-left coronary bypass systems are constructed using computational fluid-dynamics software (Fluent 6.0.1). To have a better understanding of the flow dynamics at specific time instants of the cardiac cycle, quasi-steady flow simulations are performed, using a finite-volume approach. The data input to the models are the physiological measurements of flow-rates at (i) the aortic entrance, (ii) the ascending aorta, (iii) the left coronary artery, and (iv) the right coronary artery. RESULTS: The flow field and the wall shear stress are calculated throughout the cycle, but reported in this paper at two different instants of the cardiac cycle, one at the onset of ejection and the other during mid-diastole for both the right and left aorto-coronary bypass graft models. Plots of velocity-vector and the wall shear stress distributions are displayed in the aorto-graft-coronary arterial flow-field domain. We have shown (i) how the blocked coronary artery is being perfused in systole and diastole, (ii) the flow patterns at the two anastomotic junctions, proximal and distal anastomotic sites, and (iii) the shear stress distributions and their associations with arterial disease. CONCLUSION: The computed results have revealed that (i) maximum perfusion of the occluded artery occurs during mid-diastole, and (ii) the maximum wall shear-stress variation is observed around the distal anastomotic region. These results can enable the clinicians to have a better understanding of vein graft disease, and hopefully we can offer a solution to alleviate or delay the occurrence of vein graft disease

The cryo-EM structure of the bacterial flagellum cap complex suggests a molecular mechanism for filament elongation

The bacterial flagellum is a remarkable molecular motor, whose primary function in bacteria is to facilitate motility through the rotation of a filament protruding from the bacterial cell. A cap complex, consisting of an oligomer of the protein FliD, is localized at the tip of the flagellum, and is essential for filament assembly, as well as adherence to surfaces in some bacteria. However, the structure of the intact cap complex, and the molecular basis for its interaction with the filament, remains elusive. Here we report the cryo-EM structure of the Campylobacter jejuni cap complex, which reveals that FliD is pentameric, with the N-terminal region of the protomer forming an extensive set of contacts across several subunits, that contribute to FliD oligomerization. We also demonstrate that the native C. jejuni flagellum filament is 11-stranded, contrary to a previously published cryo-EM structure, and propose a molecular model for the filament-cap interaction

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Intrapericardial Delivery of Gelfoam Enables the Targeted Delivery of Periostin Peptide after Myocardial Infarction by Inducing Fibrin Clot Formation

Background: Administration of a recombinant peptide of Periostin (rPN) has recently been shown to stimulate cardiomyocyte proliferation and angiogensis after myocardial infarction (MI). However, strategies for targeting the delivery of rPN to the heart are lacking. Intrapericardial administration of drug-eluting hydrogels may provide a clinically viable strategy for increasing myocardial retention, therapeutic efficacy, and bioactivity of rPN and to decrease systemic re-circulation. Methods and Results: We investigated the ability of intrapericardial injections of drug-eluting hydrogels to deliver and prolong the release of rPN to the myocardium in a large animal model of myocardial infarction. Gelfoam is an FDA-approved hemostatic material commonly used in surgery, and is known to stimulate fibrin clot formation. We show that Gelfoam disks loaded with rPN, when implanted within the pericardium or peritoneum of mammals becomes encapsulated within a non-fibrotic fibrin-rich hydrogel, prolonging the in vitro and in vivo release of rPN. Administration into the pericardial cavity of pigs, following a complete occlusion of the left anterior descending artery, leads to greater induction of cardiomyocyte mitosis, increased cardiomyocyte cell cycle activity, and enhanced angiogenesis compared to direct injection of rPN alone. Conclusions: The results of this study suggest that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot formation, can be used to effectively deliver rPN to the myocardium in a clinically relevant model of myocardial infarction. The work presented here should enhance the translational potential of pharmaceutical-based strategies that must be targeted to the myocardium

Evaluation of Protective Efficacy of Respiratory Syncytial Virus Vaccine against A and B Subgroup Human Isolates in Korea

Human respiratory syncytial virus (HRSV) is a significant cause of upper and lower respiratory tract illness mainly in infants and young children worldwide. HRSV is divided into two subgroups, HRSV-A and HRSV-B, based on sequence variation within the G gene. Despite its importance as a respiratory pathogen, there is currently no safe and effective vaccine for HRSV. In this study, we have detected and identified the HRSV by RT-PCR from nasopharyngeal aspirates of Korean pediatric patients. Interestingly, all HRSV-B isolates exhibited unique deletion of 6 nucleotides and duplication of 60 nucleotides in the G gene. We successfully amplified two isolates (‘KR/A/09-8’ belonging to HRSV-A and ‘KR/B/10-12’ to HRSV-B) on large-scale, and evaluated the cross-protective efficacy of our recombinant adenovirus-based HRSV vaccine candidate, rAd/3xG, by challenging the immunized mice with these isolates. The single intranasal immunization with rAd/3xG protected the mice completely from KR/A/09-8 infection and partially from KR/B/10-12 infection. Our study contributes to the understanding of the genetic characteristics and distribution of subgroups in the seasonal HRSV epidemics in Korea and, for the first time, to the evaluation of the cross-protective efficacy of RSV vaccine against HRSV-A and -B field-isolates

How do informal information sources influence women’s decision-making for birth? A meta-synthesis of qualitative studies

Background: Women approach birth using various methods of preparation drawing from conventional healthcare providers alongside informal information sources (IIS) outside the professional healthcare context. An investigation of the forms in which these informal information sources are accessed and negotiated by women, and how these disconnected and often conflicting elements influence women’s decision-making process for birth have yet to be evaluated. The level of antenatal preparedness women feel can have significant and long lasting implications on their birth experience and transition into motherhood and beyond. The aim of this study was to provide a deeper understanding of how informal information sources influence women’s preparation for birth. Methods: Seven electronic databases were searched with predetermined search terms. No limitations were imposed for year of publication. English language studies using qualitative methods exploring women’s experiences of informal information sources and their impact upon women’s birth preparation were included, subject to a quality appraisal framework. Searches were initiated in February 2016 and completed by March 2016. Studies were synthesised using an interpretive meta-ethnographic approach. Results: Fourteen studies were included for the final synthesis from Great Britain, Australia, Canada and the United States. Four main themes were identified: Menu Birth; Information Heaven/Hell; Spheres of Support; and Trust. It is evident that women do not enter pregnancy as empty vessels devoid of a conceptual framework, but rather have a pre-constructed embodied knowledge base upon which other information is superimposed. Allied to this, it is clear that informal information was sought to mitigate against the widespread experience of discordant information provided by maternity professionals. Conclusion: Women’s access to the deluge of informal information sources in mainstream media during pregnancy have significant impact on decision making for birth. These informal sources redefine the power dynamic between women and maternal healthcare providers, simultaneously increasing levels of anxiety and challenging women’s pre- existing ideations and aspirations of personal birth processes. A lack of awareness by some professionals of women’s information seeking behaviours generates barriers to women-centred support, leaving an experience expectation mismatch unchecked

Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin

<p>Abstract</p> <p>Background</p> <p>The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC.</p> <p>Methods</p> <p>Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells.</p> <p>Results</p> <p>MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively).</p> <p>Conclusions</p> <p>The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.</p

The Effect of DNA-Dependent Protein Kinase on Adeno-Associated Virus Replication

BACKGROUND: DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the roles of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased replication of AAV in MO59K and 293 cells. Southern blot analysis showed that replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to-tail junction was low or undetectable suggesting AAV-ITR self-priming is the major mechanism for rAAV DNA replication. In an in vitro replication assay, anti-Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80) was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV-ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively, our results showed that that DNA-PK enhances rAAV replication through the interaction of Ku proteins and AAV-ITRs