Pattern Of Vasculature Research Articles

Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension

Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.

Exploring the diversity of galls on Artemisia indica induced by Rhopalomyia species through morphological and transcriptome analyses.

Plant galls generated by insects have highly organized structures, providing nutrients and shelter to the insects living within them. Most research on the physiological and molecular mechanisms of gall development has focused on single galls. To understand the diversity of gall development, we examined five galls with different morphologies generated by distinct species of Rhopalomyia (gall midge; Diptera: Cecidomyiidae) on a single host plant of Artemisia indica var. maximowiczii (Asteraceae). Vasculature developed de novo within the galls, indicating active transport of nutrients between galls and the host plant. Each gall had a different pattern of vasculature and lignification, probably due to differences in the site of gall generation and the gall midge species. Transcriptome analysis indicated that photosynthetic and cell wall-related genes were down-regulated in leaf and stem galls, respectively, compared with control leaf and stem tissues, whereas genes involved in floral organ development were up-regulated in all types of galls, indicating that transformation from source to sink organs occurs during gall development. Our results help to understand the diversity of galls on a single herbaceous host plant.

Integration of Clinical Trial Spatial Multiomics Analysis and Virtual Clinical Trials Enables Immunotherapy Response Prediction and Biomarker Discovery.

Due to the lack of treatment options, there remains a need to advance new therapeutics in hepatocellular carcinoma (HCC). The traditional approach moves from initial molecular discovery through animal models to human trials to advance novel systemic therapies that improve treatment outcomes for patients with cancer. Computational methods that simulate tumors mathematically to describe cellular and molecular interactions are emerging as promising tools to simulate the impact of therapy entirely in silico, potentially greatly accelerating delivery of new therapeutics to patients. To facilitate the design of dosing regimens and identification of potential biomarkers for immunotherapy, we developed a new computational model to track tumor progression at the organ scale while capturing the spatial heterogeneity of the tumor in HCC. This computational model of spatial quantitative systems pharmacology was designed to simulate the effects of combination immunotherapy. The model was initiated using literature-derived parameter values and fitted to the specifics of HCC. Model validation was done through comparison with spatial multiomics data from a neoadjuvant HCC clinical trial combining anti-PD1 immunotherapy and a multitargeted tyrosine kinase inhibitor cabozantinib. Validation using spatial proteomics data from imaging mass cytometry demonstrated that closer proximity between CD8 T cells and macrophages correlated with nonresponse. We also compared the model output with Visium spatial transcriptomics profiling of samples from posttreatment tumor resections in the clinical trial and from another independent study of anti-PD1 monotherapy. Spatial transcriptomics data confirmed simulation results, suggesting the importance of spatial patterns of tumor vasculature and TGFβ in tumor and immune cell interactions. Our findings demonstrate that incorporating mathematical modeling and computer simulations with high-throughput spatial multiomics data provides a novel approach for patient outcome prediction and biomarker discovery. Significance: Incorporating mathematical modeling and computer simulations with high-throughput spatial multiomics data provides an effective approach for patient outcome prediction and biomarker discovery.

The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade.

Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas. We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid-Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma. The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas. This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.

PVN predisposes microglia to be susceptible to hemodynamic signals and promote sympathetic excitation in hypertension

Hypertension is usually accompanied with an elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not fully understood. Recent advances reveal that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels, and found that microglia in the hypothalamic paraventricular nucleus (PVN) were early responders to hypertensive challenges. PVN is the central hub for maintaining cardiovascular function via regulation of fluid balance and sympathetic outflow. Comprehensive vasculature analyses unveiled that PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology among brain regions. As such, PVN is susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. ATP ligation to microglial P2Y12 receptor is responsible for the microglial accumulation and activation in the PVN. Both pharmacological blockade and genetic ablation of microglial P2Y12 could substantially restrain blood pressure increase under hypertensive challenge. Together, these findings disclose that a unique vasculature pattern results in the vulnerability of PVN pre-sympathetic neurons to hypertension-associated inflammatory insults, which is mediated by microglia. NSFC82170441. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enhanced depth imaging optical coherence tomography features of two types of Vogt-Koyanagi-Harada disease: fuzzy or lost pattern of the choroidal vasculature is of diagnostic value.

This study aimed to compare enhanced depth imaging optical coherence tomography (EDI-OCT) features of exudative retinal detachment (ERD) type and optic disc (OD) swelling type Vogt-Koyanagi-Harada (VKH) disease. Hospitalized VKH patients were retrospectively reviewed and classified into the ERD type and the OD swelling type. The EDI-OCT features were then analyzed. The study included 32 ERD type and 15 OD swelling type VKH patients at the acute uveitis stage. The interval between the onset of ocular symptoms and the start of treatment in OD swelling type VKH disease was significantly longer compared to the ERD type (p < 0.001). A fuzzy or lost pattern of the choroidal vasculature was observed in 100% of VKH patients of both types. Moreover, high frequencies (greater than or equal to 50%) of fluctuations in the internal limiting membrane, interdigitation zone disruption, ERD, retinal pigment epithelium (RPE) folds, and ellipsoid zone disruption were observed in both types. Patients with OD swelling type VKH disease exhibited higher frequencies of OD swelling and hyperreflective substances above the RPE (p < 0.001 and p = 0.003, respectively), with lower frequencies of ERD and bacillary layer detachment (p = 0.012 and p < 0.001, respectively). At the convalescence stage, changes in the EDI-OCT images of 10 ERD type and 5 OD swelling type VKH patients were analyzed. The frequencies of the OCT features decreased with similar trends in both types of VKH disease. Although ERD type and OD swelling type VKH disease have their own unique characteristics, they share common EDI-OCT features. The Fuzzy or lost pattern of the choroidal vasculature that indicates choroidal inflammation may serve as a diagnostic aid for VKH disease, especially for the OD swelling type and the early-stage ERD type.

Abstract 2312: Integrating spatial multi-omics data with spatial quantitative pharmacology (spQSP) model to simulate human neoadjuvant immunotherapy clinical trial of hepatocellular carcinoma

Abstract Human clinical trials provided tremendous insights to advance novel systemic therapies and to improve treatment outcomes for cancer patients. The few durable treatment options have led to a critical need to advance new therapeutics in hepatocellular carcinoma (HCC). Recent human clinical trials have demonstrated that new combination of immunotherapeutic regimens provide augmented clinical response in a subset of patients. Computational methods that can simulate tumors from mathematical equations describing cellular and molecular interactions are emerging as promising tools to simulate the impact of therapies entirely in silico. To facilitate designing dosing regimens and selecting potential predictive biomarkers, we developed a new computational model to track tumor progression at organ scale while reflecting the spatial heterogeneity in the tumor at cellular and molecular scale in HCC. This computational model is called a spatial quantitative systems pharmacology (spQSP) platform and it is also designed to simulate the effects of combination immunotherapy. The model is first calibrated using clinical outcomes and measured immune cell densities based on recent neoadjuvant HCC clinical trial combining anti-PD-1 immunotherapy and a multitargeted tyrosine kinase inhibitor (TKI) cabozantinib (NCT03299946). Then, we validate the results from the spQSP model by leveraging real-world spatial multi-omics data from the same clinical trial. The model output is compared with spatial data from Imaging Mass Cytometry (IMC). Both IMC data and simulation results suggest closer proximity between CD8 T cell and Arginase 1 (Arg1) positive macrophages among non-responders while the reverse trend was observed for responders. We also compared the model output with Visium spatial transcriptomics analyses of samples from post-treatment tumor resections in the original clinical trial. Both spatial transcriptomic data and simulation results identify the role of spatial patterns of tumor vasculature and TGFβ in tumor and immune cell interactions. To our knowledge, this is the first spatial tumor model for virtual clinical trials at a molecular and cellular scale that is grounded in high-throughput spatial multi-omics data from a human clinical trial. Citation Format: Shuming Zhang, Atul Deshpande, Babita K. Verma, Hanwen Wang, Haoyang Mi, Long Yuan, Won Jin Ho, Elizabeth M. Jaffee, Qingfeng Zhu, Robert A. Anders, Mark Yarchoan, Luciane T. Kagohara, Elana J. Fertig, Aleksander S. Popel. Integrating spatial multi-omics data with spatial quantitative pharmacology (spQSP) model to simulate human neoadjuvant immunotherapy clinical trial of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2312.

Dermoscopic features of pigmented basal cell carcinoma according to size.

Basal cell carcinoma (BCC), the most common skin cancer in humans, requires early detection. Dermoscopy enhances diagnostic accuracy through a noninvasive approach. Pigmented BCC (pBCC) is characterized by distinctive dermoscopic features, including the presence of pigmented globules or nests. While dermoscopic features of large pBCC (size >6 mm) have been extensively studied, limited data are available on small pBCC (size ≤6 mm) and its relationship with tumor progression. Dermoscopic images of histologically proven pBCCs were collected between 2014 and 2022 at Hualien Tzu Chi Hospital. Each image was analyzed for patterns of pigmentation, vasculature, and epidermal and dermal structures. Statistical analysis was performed to compare the differences according to the size and the trend during tumor progression. In total, 135 pBCCs (48 small and 87 large) were included. Pigment structures were present in all cases. Short fine telangiectasia and small erosions constituted over 85% of the cases, showing no significant distinction between small and large pBCCs, nor any specific pattern correlating with tumor enlargement. The number of arborizing vessels, ulcerations, and shiny white structures showed an increasing trend associated with size progression. Arborizing vessels appeared when tumor size exceeded 6 mm. This study provides a dynamic interpretation of the dermoscopic features of pBCC according to size enlargement. Short fine telangiectasia and small erosions are highly important features for the early diagnosis of small pBCCs. Arborizing vessels, ulceration, and shiny white structures are more frequent in large pBCCs, and they increase in association with tumor progression.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

Effective seed cake extract of O. sanctum inducing the p53 dependent apoptotic pathway in oral cancer cells

Objective Present study was to observe the therapeutic aspects of seed cake extracts of Ocimum sanctum against the oral cancer cell line with the activation of p53 apoptotic pathway. Method Seed cake extracts were characterized using GC-MS analysis. Cytotoxic activity was observed on KB cells and L929 cell through MTT assay and scratch assay. Antioxidant activity on KB cells were determined using enzymatic and non enzyme content in the treated cells. Chick chorioallantoic membrane (CAM) was established to check the presence of blood vessel formation and neuvasculature pattern in the treated fertilized eggs. DNA fragmentation and gene expression studies were also determined in the treated cells to check the upregulation of apoptotic pathways. Results GC-MS analysis confirmed alkaloids, phenols, and many. The cytotoxic activity showed maximum antiproliferative potential with aqueous extract, whereas no cytotoxic effect was observed on L929 cells. The ethanolic and aqueous extract has shown a greater SI value. Scratch assay has signified that aqueous extract has a lower migration rate of KB cells. Aqueous extract showed maximum enzymatic activity and lower malondialdehyde content in cells treated with ethanolic extract. CAM model confirmed that eggs treated with aqueous extract has shown inhibition of vasculature pattern and dissolutions of blood vessels. DNA Fragmentation and Gene expression studies confirmed maximum fold in the KB cell treated with an aqueous extract of seed cake leading to activation of p53 dependent apoptotic pathway. Conclusion The potent therapeutic properties of seed cake extracts have been proven, and they can be used as herbal treatments to prevent oral cancer.

Evaluating Tumor Hypoxia Radiosensitization Via Electron Paramagnetic Resonance Oxygen Imaging (EPROI).

Tumor hypoxia contributes to aggressive phenotypes and diminished therapeutic responses to radiation therapy (RT) with hypoxic tissue being 3-fold less radiosensitive than normoxic tissue. A major challenge in implementing hypoxic radiosensitizers is the lack of a high-resolution imaging modality that directly quantifies tissue-oxygen. The electron paramagnetic resonance oxygen-imager (EPROI) was used to quantify tumor oxygenation in two murine tumor models: E0771 syngeneic transplant breast cancers and primary p53/MCA soft tissue sarcomas, with the latter autochthonous model better recapitulating the tumor microenvironment in human malignancies. We hypothesized that tumor hypoxia differs between these models. We also aimed to quantify the absolute change in tumor hypoxia induced by the mitochondrial inhibitor papaverine (PPV) and its effect on RT response. Tumor oxygenation was characterized in E0771 and primary p53/MCA sarcomas via EPROI, with the former model also being quantified indirectly via diffuse reflectance spectroscopy (DRS). After confirming PPV's effect on hypoxic fraction (via EPROI), we compared the effect of 0 versus 2 mg/kg PPV prior to 20 Gy on tumor growth delay and survival. Hypoxic sarcomas were more radioresistant than normoxic sarcomas (p=0.0057, 2-way ANOVA), and high baseline hypoxic fraction was a significant (p=0.0063, Cox Regression Model) hazard in survivability regardless of treatment. Pre-treatment with PPV before RT did not radiosensitize tumors in the sarcoma or E0771 model. In the sarcoma model, EPROI successfully identified baseline hypoxic tumors. DRS quantification of total hemoglobin, saturated hemoglobin, changes in mitochondrial potential and glucose uptake showed no significant difference in E0771 tumors pre- and post-PPV. EPROI provides 3D high-resolution pO2 quantification; EPR is better suited than DRS to characterize tumor hypoxia. PPV did not radiosensitize E0771 tumors nor p53/MCA sarcomas, which may be related to the complex pattern of vasculature in each tumor. Additionally, understanding model-dependent tumor hypoxia will provide a much-needed foundation for future therapeutic studies with hypoxic radiosensitizers.

Abstract P412: Microglia Via P2y 12 Transmit Hemodynamic Signal To Promote Sympathetic Activation In Hypertension

Hypertension is characterized by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not fully understood. Recent studies reveal that microglia highly involve in the regulation of sympathetic neuronal activity in the hypothalamic paraventricular nucleus (PVN). In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels, and found that microglia in the PVN were the earliest responders to hypertensive challenge. Comprehensive vasculature analysis unveiled that PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology compared to other brain regions. PVN is susceptible to the penetration of ATP derived from the vasculature in response to hemodynamic disturbance upon pressor challenge. Furthermore, either pharmacological blockade or genetic ablation of microglia P2Y12 could substantially restrain pressor response under hypertensive stimulation Together, these findings suggest that a unique vasculature pattern endows PVN with susceptibility to hypertension-associated hemodynamic insults, which is mediated by microglia.

Branching Patterns of Human Coronary Vasculature and Its Clinical Importance

Branching Patterns of Human Coronary Vasculature and Its Clinical Importance

Understanding floral variation in Leiothrix (Poales: Eriocaulaceae): anatomy, development and insights into pollination

Abstract Leiothrix differs from other genera of Eriocaulaceae by having pistillate flowers with nectariferous and stigmatic branches that diverge at different heights on the style and staminate flowers with free or fused petals. To understand the ontogenetic processes that result in these morphological variations, we studied the development and floral vasculature in six species of the genus. In pistillate flowers, the nectariferous branches, which are in a carinal position, correspond to the apex of the carpels, whereas the stigmatic branches, in a commissural position, are formed by the marginal tissues of the carpels and initiate later than the nectariferous branches. The upper margins of the carpels elongate, forming a tubular structure that raises the stigmatic branches; the greater its development, the greater the distance between the stigmatic and nectariferous branches. In staminate flowers, the fusion of the petals appears to be post-genital in the median and apical portions and congenital in the more basal portion. Despite the differences in floral development, Leiothrix shares the same pattern of floral vasculature with other genera of Eriocaulaceae, exhibiting a central vascular plexus in the receptacle from which a single trace diverges for each sepal, petal and stamen. The staminodes are not vascularized. The dorsal carpellary bundles supply the nectariferous branches, but the ventral carpel bundles are reduced and are not involved in the supply of the ovules and stigmas. The differences in the height of insertion of the nectariferous branches are probably the result of selective pressure exerted by different groups of pollinating insects. Our hypothesis is that species in which the nectariferous branches are inserted below the stigmatic branches, and are therefore less accessible, exhibit a more specialized pollination system. The absence of nectariferous branches in L. angustifolia indicates secondary loss probably associated with spontaneous geitonogamy.

Reply: The Versatility of the Pedicled Medial Sural Artery Perforator Flap: From Simple to Its Chimeric Pattern and Clinical Experience with 37 Cases.

We read with great interest the reply to our article1 on the use of the pedicled medial sural artery perforator (MSAP) flap by our esteemed colleagues, Dr. Sadeghi and Dr. Pandey. We would like to offer our thoughts on their points of discussion. We thank our colleagues for highlighting the use of one MSAP skin paddle for donor-site closure as described in our article. As with other free flaps, donor-site closure plays an important role and can heavily influence the overall patient result. Utilizing MSAP free flaps can result in donor-site–specific complications, as outlined in the Discussion section of our article. In our experience, the majority of MSAP donor sites can be closed primarily without tension. However, in cases where primary donor-site closure is not possible, using a pedicled MSAP flap based on a second perforator can be an elegant solution to cover the donor site. In our reported cases, this has resulted in both functional and aesthetically pleasing results regarded as superior to a skin graft alternative. We recognize the importance of the medial sural artery branching pattern when using the MSAP flap, as mentioned by our colleagues. The vasculature pattern of the MSAP must be considered during dissection, and the classification introduced by Dusseldorp et al.2 can provide guidance for the operating surgeon. Indeed, the option to use the gastrocnemius muscle flap as a backup option after a failed MSAP flap is dependent on adequate vascular supply and, therefore, branching pattern. The recent report of two cases of gastrocnemius muscle flap necrosis by Tsou et al.3 underscores this issue. We agree with them that this is a rare complication of MSAP harvest, and careful dissection in combination with Doppler ultrasound can further minimize the risk.3 With regard to the synchronous harvest of functional tissue with the MSAP flap, we would like to thank our colleagues for raising another interesting topic. As described in our article, the chimeric form of the MSAP flap allows for harvest of (multiple) skin islands and independent muscular parts. While, to date, we have not harvested any other functional tissues with the flap, we recognize that the synchronous harvest of tendon, nerve, and vein grafts from the same donor site4 provides an additional range of reconstructive options. This increases the versatility of the donor site, providing a favorable single-stage reconstruction, and might even have applications beyond the described context of hand defects. Disclosure The authors have no financial interest to declare in relation to the content of this communication. No funding was received for this work. Timo Rodi, MD, MScMario F. Scaglioni, MDDepatment of Hand and Plastic Surgery Luzerner KantonsspitalLucerne, Switzerland

Dilated choroidal vascular channels in pachychoroid neovasculopathy.

To elucidate the pattern of the choroidal vasculature in exudative pachychoroid neovasculopathy (PNV) and its correlation with the clinical course and treatment outcomes. The retrospective study included consecutive patients in National Taiwan University Hospital between 2014 and 2020 who fulfilled the criteria for exudative PNV defined as active type 1 macular neovascularization (MNV) on optical coherence tomography angiography (OCTA) and with leakage on fluorescein angiography (FA) or indocyanine green angiography (ICGA) associated with pachychoroid features. The corrected distance visual acuity (CDVA), FA, ICGA, and OCT images obtained by Optovue (Optovue Inc, Freemont CA, USA) spectral domain OCT were evaluated at baseline and various time points during the 12-month treatment period. The correlations between the choroidal vascular patterns, specifically those with or without dilated choroidal vascular channels (DCVC) revealed by ICGA, and baseline characteristics and treatment outcomes were evaluated using multiple regression models. The study enrolled 34 eyes of 31 patients. The average age was 59.0± 9.3 years, and 20 participants were men. ICGA revealed DCVCs in 21 eyes, while the remaining 13 eyes did not have DCVCs. At baseline, DCVC group was older (p= 0.03) and had a longer duration of visual symptoms (p= 0.02), with a higher vessel density (defined as the percentage of the measured area occupied by flow area) of MNV (p= 0.04), higher proportion of ellipsoid zone disruption (p= 0.01), and poorer CDVA (p= 0.03). After the 12-month treatment period, the frequency of requirement of anti-VEGF injections (p< 0.01) was higher, and the risk for CDVA <20/40 was higher (adjusted OR: 5.29, 95% CI: 1.24-22.48, p= 0.02) in eyes with DCVCs. For PNV, eyes with DCVCs were associated with higher vessel density of macular neovascularization and poorer CDVA at baseline, and had poorer visual and anatomical outcomes although more anti-VEGF injections were given.

CT Visualization of Vasculature Channels in Modern and Fossil Sloth Ungual Claws

One of the interesting features of modern sloths is the vasculature patterns of their upper and lower limbs. Even though sloths are endothermic like other mammals, their mean body temperature tends to be lower, more variable, and more linked to the ambient temperature than other placental mammals. Like some other mammals from environments with temperature extremes, they possess rete arteriovenous bundles, which work as an effective heat exchange mechanism, where heat from distally flowing arterial blood is transferred to proximally flowing venous blood. This minimizes the heat loss from the extremities while still maintaining blood flow. The temperature gradient increases in the rete system when the animal’s core temperature decreases, which cools the limbs and preserves core body heat. When the body temperature rises the flow through the superficial venous system increases, which promotes heat loss and body cooling.This begs the question of how this complex vasculature system may or may not extend to the distal phalanges and claws of the sloth, perhaps their most distinctive feature. One possibility could be that to work with the limb cooling function of the rete system, the distal phalanx and claw may be poorly vascularized so as not to increase chances for heat loss. However, considering the extensive and important use of their claws, they may require extensive vascularization to withstand the large amount of stress they are often under. This study uses Micro CT scans of sloth ungual phalanges to visualize their vascular channels. In both modern and extinct giant ground sloths, vascular networks through the bone of the ungual phalanx are quite extensive, and are very clearly linked to externally visible channels and impressions left by the proper digital arteries. In ground sloths these internal vascular channels quickly branch on either side and continue distally, letting off smaller branches as they go. These channels are rather large, even appearing to be artificial drill holes on one specimen that has the distal end broken off. Modern sloths show a similar pattern, but their vascular channels take up proportionally less space in the bone than in the giant ground sloths. This difference may be due extinct giant ground sloths’ more varied use of their claws. These complex patterns show that sloth claws require a significant blood supply, and may indicate that the rete system is effective enough that by the time the arterial blood gets to the distal phalanx it has been sufficiently cooled to not be a significant source of heat loss.

Anatomical classification of middle rectal arteries regarding detailed vasculature patterns.

This study aimed to clarify the anatomy of middle rectal artery and pelvic vasculature patterns, and to provide schematic information in a manner applicable to the total mesorectal excision. Forty sides of pelvis from 20 formalin-embalmed cadavers (10 male, 10 female) were dissected, and all the pelvic vasculatures from the internal iliac artery were investigated, focusing on the middle rectal artery. Middle rectal arteries were classified into major types depending on their vascular origins. Each type was subdivided into minor types according to variability of the pelvic vasculature. A middle rectal artery was identified in 18 out of 20 cadavers, and in 25 out of 40 pelvic sides. In most cases, the middle rectal artery originated from the internal pudendal artery or inferior gluteal artery. These two arteries arose directly from the anterior trunk of the internal iliac artery or were bifurcated from the gluteal-pudendal trunk. In rare cases, these arteries arose from the posterior trunk of the internal iliac artery. The other origins of the middle rectal artery included the gluteal pudendal trunk, inferior vesical artery, internal iliac artery, obturator artery, and the prostatic artery, and the pelvic vasculatures in these cases also presented variability. The detailed anatomical findings related to the middle rectal artery and pelvic vasculatures are noteworthy for their improved clinical applicability.

Assessment of angiogenesis-related parameters in juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be observed clinically. Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n = 30), acute anterior uveitis (AAU; n = 18), and primary open angle glaucoma (POAG; n = 20) were obtained during trabeculectomy or cataract surgery. Samples were analyzed by RNA-Seq, qRT-PCR, LC-IMS, Western-Blot, and LEGENDplex™ analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA). RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG, p > 0.05). LC-IMS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which Angiopoetin, Lumican and Decorin were associated with angiogenesis and showed increased (p > 0.05) expression on Western-Blot analysis. LEGENDplex™ analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIA patients with treatment-refractory complicated course of uveitis. Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.

Pneumatosis intestinalis: a rare endoscopic feature of colonic ischemia.

A 71-year-old male was admitted on intensive care unit after endovascular aneurysm repair of ruptured infrarenal abdominal aortic aneurysm. 2 weeks later, he had multiple episodes of bloody diarrhea. Colonoscopy revealed diffuse dusky mucosal coloration with loss of vasculature pattern, diseased haustrations, and diffuse areas of pneumatosis, suggestive of severe colonic ischemia.