The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels. These findings highlight a previously unknown central nervous system communication pathway, which, like that of the pituitary portal system, could allow neurosecretions to reach nearby target sites in OVLT, avoiding dilution in the systemic blood. In both of these brain portal pathways, the target sites relay signals broadly to both the brain and the rest of the body.

Congenital portosystemic shunts (CPSSs) are rare vascular anomalies characterized by abnormal connections between the portal/splanchnic veins and the systemic veins. CPSSs often occur as an isolated congenital anomaly, but they can also coexist with congenital heart disease (CHD). Owing to their myriad consequences on multiple organ systems, familiarity with CPSS is of tremendous importance to the care of patients with CHD. The rationale and timing for interventions to embolize CPSS in this scenario are discussed. Specific shunt embolization techniques are beyond the scope of this article.

Neurological symptoms that occur after treatment of portosystemic shunts, in cats, known as post-attenuation neurological signs (PANS) can be quite severe. This study seeks to analyze a better understanding of the neurological outcomes that result from reducing portosystemic shunts in felines and provide insights that could guide future clinical approaches and treatment strategies for congenital portosystemic shunts (CPSS).The research utilized the MOOSE Checklist as a guide. PubMed/MEDLINE, Web of Science ScienceDirect, Embase, Scopus, ProQuest, and Google Scholar were used. The study investigated diversity using variance, Cochran Q tests with Applied fixed effects, and random effects models. A meta-regression model identified contributors. Eggers test funnel plot and Beggs test for asymmetry addressed publication bias. 12 high-quality studies were discovered from 664 research papers. This research covered years, shunt morphology, and surgery. PANS occurred 38.9 % of the time in cats, while PAS occurred 20.2 %. The overall PANS mortality rate was 17 %, while PAS was 37.2 %. The complete ligation technique was most common in subgroup analysis. PANS occurrence ranged from 26.8 % to 56.5 % in cats with congenital extrahepatic portosystemic shunts The cause of PANS in cats is still unknown, and there is only limited evidence to justify the use of preventive antiepileptic medications such as levetiracetam. The treatment primarily aims to control neurologic symptoms, and the long-term outlook varies, with the potential for the reappearance of symptoms.

BACKGROUND: Dogs with congenital intrahepatic portosystemic shunt (IHPSS) are predisposed to gastrointestinal inflammation, ulceration, and bleeding, unlike dogs with congenital extrahepatic portosystemic shunt (EHPSS). Limited information is available about hematologic differences between dogs with IHPSS and dogs with EHPSS.
OBJECTIVE: Compare hemogram variables between dogs with IHPSS and EHPSS. We hypothesized that hematologic variables would differ between the 2 populations, with a higher frequency and severity of anemia and microcytosis in dogs with IHPSS.
METHODS: Twenty-six client-owned dogs with IHPSS and 35 client-owned dogs with EHPSS.
METHODS: Retrospective cross-sectional study. Dogs were included if a CBC was performed before shunt attenuation. Contingency analysis was performed to determine if the frequency of clinical signs and of hematologic variables below the reference range differed between groups. Hematologic and selected biochemical variables were compared between groups using an analysis of covariance with age as a covariate.
RESULTS: Gastrointestinal clinical signs (IHPSS, 81% vs EHPSS, 34%; P = .01), anemia (31% vs 6%; P = .01), microcytosis (77% vs 29%; P = .002), and hypochromia (77% vs 49%; P = .03) were more common in dogs with IHPSS than in dogs with EHPSS. Dogs with IHPSS had lower packed cell volume (34% vs 41%, P = .04), hemoglobin concentration (11.5 g/dL vs 13.7 g/dL, P = .03), mean corpuscular volume (57 fL vs 65 fL; P = .001), and mean corpuscular hemoglobin concentration (32 g/dL vs 33 g/dL; P = .04) than dogs with EHPSS.
CONCLUSIONS: Dogs with IHPSS had a higher frequency of anemia, microcytosis, and hypochromia and exhibited more gastrointestinal clinical signs.

The prevalence of anatomical-based subtypes of feline congenital extrahepatic portosystemic shunts (EHPSS) has not been completely elucidated. The goal of this study was to use CT angiography to create an anatomical-based nomenclature system for feline congenital EHPSS. Additionally, subjective portal perfusion scores were generated to determine if intrinsic portal vein development was associated with different shunt conformations or patient age at the time of CT. The SVSTS and VIRIES list services were used to recruit cases. Data collected included patient DOB, gender, breed, weight, CT date, and reported diagnosis. Shunts were classified based upon (1) the shunt portal vessel(s) of origin, (2) the shunt systemic vessel(s) of insertion, and (3) any substantial portal vessels contributing to the shunt. Additionally, hepatic portal perfusion was subjectively scored between 1 (poor/none) and 5 (good/normal) based on the caliber of the intrahepatic PVs. A total of 264 CT scans were submitted from 29 institutions. Due to exclusion criteria, 33 (13%) were removed, leaving 231 CT scans to be included. Twenty-five different EHPSS anatomies were identified with five classifications accounting for 78% of all shunts (LGP [53%], LGC-post [11%], LCG [7%], LGC-pre [4%], and PC [4%]). Shunt origin involved the left gastric vein in 75% of the described classifications. Significant differences were identified among the five most common shunt types with respect to age at the time of CT scan (P = .002), breed (P < .001), and subjective portal perfusion score (P < .001). This refined anatomical classification system for feline EHPSS may enable improved understanding, treatment comparisons, and outcome prediction for cats with these anomalies.

Lymphatic vessel development studies in mice and zebrafish models have demonstrated that lymphatic endothelial cells (LECs) predominantly differentiate from venous endothelial cells via the expression of the transcription factor Prox1. However, LECs can also be generated from undifferentiated mesoderm, suggesting potential diversity in their precursor cell origins depending on the organ or anatomical location. Despite these advances, recapitulating human lymphatic malformations in animal models has been difficult, and considering lymphatic vasculature function varies widely between species, analysis of development directly in humans is needed. Here, we examined early lymphatic development in humans by analyzing the histology of 31 embryos and three 9-week-old fetuses. We found that human embryonic cardinal veins, which converged to form initial lymph sacs, produce Prox1-expressing LECs. Furthermore, we describe the lymphatic vessel development in various organs and observe organ-specific differences. These characterizations of the early development of human lymphatic vessels should help to better understand the evolution and phylogenetic relationships of lymphatic systems, and their roles in human disease.

The accurate diagnosis of portovascular anomalies has been facilitated by improvements in diagnostic imaging technology. In humans, hepatic arterial blood flow changes in response to the reduction in portal blood flow. The hepatic arterial buffer response characterizes an intrinsic regulatory mechanism in response to reduced portal venous blood flow, which results in hepatic arterial enlargement. At the authors\' institution, enlargement of the hepatic artery has been anecdotally observed in a population of dogs with extrahepatic portosystemic shunting, consistent with previous literature that documents variability in hepatic arterial size. In this retrospective, blinded, analytical study, a hepatic artery:aorta (Ha:Ao) ratio was assessed on CT studies from 112 dogs, with (n = 43) and without (n = 69) an extrahepatic congenital portosystemic shunt in order to compare the hepatic artery size independent of body weight between the two populations. A significant increase in the Ha:Ao ratio was documented in dogs with an extrahepatic portosystemic shunt (EHPSS) compared with those dogs with no EHPSS independent of the location of shunt insertion into the systemic circulation (P < .001). Three cases had repeat CT after surgery, and all had Ha:Ao ratio reductions following treatment. The authors propose that this may be an additional imaging feature observed in dogs with an EHPSS.

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 μM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model.

BACKGROUND: The outer membrane vesicles (OMVs) derived from Porphyromonas gingivalis (P. gingivalis) have long been acknowledged for their crucial role in the initiation of periodontitis. However, the implications of P. gingivalis OMVs in the context of cardiovascular disease (CVD) remain incompletely understood. This study aimed to clarify both the impact and the underlying mechanisms through which P. gingivalis OMVs contribute to the propagation of distal cardiovascular inflammation and trauma.
METHODS: In this study, various concentrations (0, 1.25, 2.5, and 4.5 µg/µL) of P. gingivalis OMVs were microinjected into the common cardinal vein of zebrafish larvae at 48 h post-fertilization (hpf) to assess changes in cardiovascular injury and inflammatory response. Zebrafish larvae from both the PBS and the 2.5 µg/µL injection cohorts were harvested at 30 h post-injection (hpi) for transcriptional analysis. Real-time quantitative PCR (RT-qPCR) was employed to evaluate relative gene expression.
RESULTS: These findings demonstrated that P. gingivalis OMVs induced pericardial enlargement in zebrafish larvae, caused vascular damage, increased neutrophil counts, and activated inflammatory pathways. Transcriptomic analysis further revealed the involvement of the immune response and the extracellular matrix (ECM)-receptor interaction signaling pathway in this process.
CONCLUSIONS: This study illuminated potential mechanisms through which P. gingivalis OMVs contribute to CVD. It accentuated their involvement in distal cardiovascular inflammation and emphasizes the need for further research to comprehensively grasp the connection between periodontitis and CVD.

Within the developing embryo, cells assemble and remodel their surrounding extracellular matrix during morphogenesis. Fibronectin is an extracellular matrix glycoprotein and is a ligand for several members of the Integrin adhesion receptor family. Here, we compare the expression pattern and loss of function phenotypes of the two zebrafish fibronectin paralogs fn1a and fn1b. We engineered two fluorescently tagged knock-in alleles to facilitate live in vivo imaging of the Fibronectin matrix. Genetic complementation experiments indicate that the knock-in alleles are fully functional. Fn1a-mNeonGreen and Fn1b-mCherry are co-localized in ECM fibers on the surface of the paraxial mesoderm and myotendinous junction. In 5-days old zebrafish larvae, Fn1a-mNeonGreen predominantly localizes to the branchial arches, heart ventricle, olfactory placode and within the otic capsule while Fn1b-mCherry is deposited at the pericardium, proximal convoluted tubule, posterior hindgut and at the ventral mesoderm/cardinal vein. We examined Fn1a-mNeonGreen and Fn1b-mCherry in maternal zygotic integrin α5 mutants and integrin β1a; β1b double mutants and find distinct requirements for these Integrins in assembling the two Fibronectins into ECM fibers in different tissues. Rescue experiments via mRNA injection indicate that the two fibronectins are not fully inter-changeable. Lastly, we examined cross-regulation between the two Fibronectins and find fn1a is necessary for normal Fn1b fibrillogenesis in the presomitic mesoderm, but fn1b is dispensable for the normal pattern of Fn1a deposition.