Using a large elderly population cohort, we investigated the relationship between choroid plexus (CP) volume, a potential indicator of glymphatic system activity, and lifestyle-related vascular risk and protective factors, as well as age-related changes in CP volume. This cross-sectional study included 2137 participants (median age, 70 years) who underwent 3-T MRI and vascular risk factor assessment. Factors included body mass index (BMI), systolic blood pressure (SBP), total cholesterol, hemoglobin A1c (HbA1c), smoking (Brinkman Index), and physical activity (International Physical Activity Questionnaire). Multiple regression analyses were conducted, adjusting for total intracranial volume (TIV), age, gender, and medication use. CP volume significantly increased with age (r = 0.351, p < 0.001). Among the vascular risk factors, only a higher Brinkman Index (smoking) was significantly associated with a larger CP volume in the overall analysis (β = 0.075, FDR-corrected p < 0.001). In sex-specific analyses, higher systolic blood pressure and an increased Brinkman Index were associated with larger CP volumes in males. In females, no vascular risk factors remained significant after correction for multiple comparisons. These factors explained only a small proportion of the variance in CP volume (R² = 0.013). In this large cohort of older adults, choroid plexus volume increases with age. Sex-specific analyses revealed that systolic blood pressure and smoking were significant risk factors in males, while no significant associations were found in females. However, these vascular factors explained only a small proportion of the variance in CP volume. Question How do lifestyle-related vascular risk factors like hypertension, smoking, and obesity affect choroid plexus volume, a potential indicator of glymphatic function? Findings In this elderly cohort, choroid plexus volume increased with age and was associated with smoking; males showed an additional significant association with higher blood pressure. Clinical relevance Understanding the sex-specific links between vascular risk factors and choroid plexus volume is crucial for developing targeted strategies to preserve glymphatic function and brain health in aging populations.

Precocious puberty in girls is a condition marked by the early onset of secondary sexual characteristics, with vascular factors like uterine artery pulsatility index having been suggested as potential indicators. We performed Mendelian randomization (MR) analysis using genetic instruments from large-scale genome-wide association studies (GWAS) datasets, including ebi-a-GCST008403, ukb-a-250, and ukb-b-11971, to evaluate the relationship between arterial stiffness and precocious puberty. Exposure and outcome data were sourced from the GWAS Catalog, eQTLGen, and the R11_E4_PREPUB dataset. The TwoSampleMR package was employed to assess causal relationships, with several MR methods applied, including inverse variance weighted, MR Egger, weighted median, and mode-based methods. Our analysis of arterial stiffness using ebi-a-GCST008403, ukb-a-250, and ukb-b-11971 datasets did not show a statistically significant causal relationship with precocious puberty. The IVW method showed an OR of 0.707 (p=0.885) for arterial stiffness, indicating no reliable association. The investigation into MMP2 also yielded non-significant results across all methods, with an OR of 0.778 (p=0.330) from the IVW method. However, the analysis of MMP9 revealed a significant association with precocious puberty, showing an OR of 3.89 (p=0.004) using the IVW method, and an OR of 3.96 (p=0.027) from the Weighted Median method, indicating a strong positive effect of MMP9 on precocious pubertyrisk. Our findings suggest that while arterial stiffness and other MMPs do not have a significant causal role, MMP9 may significantly increase the risk of precocious puberty ingirls.

Plants continuously produce lateral organs, such as leaves and flowers, from the shoot apical meristem (SAM). This process is guided by the accumulation of the plant hormone auxin and the polar localization of the efflux protein PIN-FORMED1 (PIN1). The transcription factor MONOPTEROS (MP) plays a crucial role in orienting PIN1 polarity, thereby facilitating auxin-driven organogenesis. In this study, we investigate genes downstream of MP that may regulate PIN1 polarity and organogenesis, discovering that the downstream vascular transcription factor TMO5 can promote PIN1 polarity convergence non-cell-autonomously and that TMO5 and its family members promote organ initiation in the SAM. By examining the role of auxin and cytokinin downstream of these genes, we provide evidence that the TMO5-like genes control PIN1 polarity and drive organogenesis by coordinating multiple hormonal signalling pathways.

Abstract BACKGROUND CNS germinoma is typically treated with combination of chemotherapy and radiotherapy, with steroids used temporarily for symptom management. METHODS We report a case of CNS germinoma initially treated with steroid monotherapy with reduction in radiographic enhancement. RESULTS A 25 year old male initially presented with polydipsia and polyurea that improved with desmopressin, consistent with central diabetes insipidus. Brain imaging was unremarkable and he was lost to follow up. 3 years later, he developed progressively worsening bitemporal scotomas, intermittent binocular horizontal diplopia, reduced visual acuity, headaches, weight gain, and sexual dysfunction. MRI brain revealed enhancement of the pituitary stalk, optic chiasm and optic nerves, floor of the third ventricle, lateral ventricles, periventricular white matter, and anterior corpus callosum and fornix with associated T2 hyperintensity within the optic chiasm and adjacent brain parenchyma. Biopsy was consistent with germinoma. He was started on a dexamethasone taper beginning at 4 mg every 6 hours and plateauing at 4 mg twice daily. 3 weeks after steroid initiation, the areas of enhancement surrounding the frontal horns of the lateral ventricles showed reduction in size. DISCUSSION Reduced tumoral enhancement with steroid monotherapy is a well-known phenomenon in CNS lymphoma and has been reported in gliomas, attributed to direct induction of apoptosis in CNS lymphoma and alterations in the blood brain barrier via suppression of vascular permeability factors in both. This case adds to the scant literature regarding change in enhancement patterns with steroid monotherapy in CNS germinomas, which is likely related to a reduction in tumoral diffuse lymphocyte infiltration with steroid administration. The reduction in enhancement seen in multiple CNS mass-like pathologies emphasizes the importance of a tissue diagnosis for germinomas, as this steroid response is transient and not indicative of true tumor regression. Definitive treatment of germinomas is combination chemotherapy and radiation.

Background: Type B acute aortic dissection (AAD) is often managed medically, with potential outcome differences by menopausal status due to hormonal and vascular factors. We evaluated the impact of menopausal status on inpatient mortality, length of stay (LOS), and total hospitalization charges. Methods: Using National Inpatient Sample data (2016–2019), we identified 3,533 women with Type B AAD ( excluding if any aortic surgical procedures) via ICD-10-CM codes, comprising 417 premenopausal (&lt;50 years) and 3,116 postmenopausal (≥50 years or any postmenopausal related codes) patients. A 1:1 nearest-neighbor propensity score matching using 20 sociodemographic and clinical covariates mitigated confounders, yielding a balanced cohort of 737 patients (369 per group). The primary outcome was inpatient mortality. Secondary outcomes were LOS and total charges. Logistic regression assessed mortality; Wilcoxon tests compared LOS and charges. Results: The matched cohort had a mean age of 53.5 years and included 44.4% White, 39.0% Black, 8.7% Hispanic, 7.9% Other. Postmenopausal women had higher odds of mortality (odds ratio [OR] 3.11, 95% CI 1.69–5.71, p&lt;0.001) in the matched cohort, consistent with the unmatched cohort (OR 4.59, 95% CI 2.82–7.46, p&lt;0.001). LOS (median 4 vs. 5 days, IQR 6 vs. 6, p=0.956) and charges (median $64,103 vs. $67,020, IQR $114,634 vs. $102,720, p=0.817) were similar for postmenopausal versus premenopausal women. Conclusion: Postmenopausal women with medically managed Type B AAD face significantly higher inpatient mortality, but similar LOS and hospitalization cost, highlighting the need for menopausal status-specific risk stratification.

Rationale: The role of BMP9 in pulmonary arterial hypertension (PAH) remains controversial. Loss-of-function GDF2 /BMP9 mutations in heritable PAH suggest its function as a vascular endothelial homeostasis factor, however, modulating BMP9 signaling in experimental pulmonary hypertension (PH) models can yield pathogenic or protective effects. The impact of BMP9 upon intracellular and intercellular angiogenic signaling cascades remains poorly understood. Methods/Results: We analyzed BMP9-mediated transcription in pulmonary microvascular endothelial cells (PMVEC) derived from controls and patients, and in the presence or absence of co-cultured pulmonary artery smooth muscle cells (PASMC). We tested recombinant BMP9, BMP9/BMP10 ligand trap ALK1-Fc, anti-BMP9, and activin/GDF ligand trap ACTRIIA-Fc in hypoxia, SUGEN5416+hypoxia (SU-Hx) and monocrotaline (MCT) experimental PH rodent models. The BMP9-regulated secretome of ECs was examined for potential modulation of PASMC phenotype and function. Inhibition of BMP9 and/or BMP10 was protective whether administered before or after the development of experimental PH, and attenuated experimental PH when administered therapeutically in the SU-Hx model. In PMVEC, BMP9 elicited expression of vasoactive genes that were also elevated in experimental PH and human PAH lungs, including EDN1, CXCL12, IGFBP4, COL18A1, VEGFA, PDGFB , and SERPINE1 , several of which were normalized in lungs of SU-Hx rats with anti-BMP9 treatment. Several of these genes required non-canonical activation of SMAD3 downstream of BMPR2, ALK1, and ENG. Promoter analysis of human ET-1 revealed cooperation of SMAD3 and SMAD1/5 binding elements is required for BMP9-mediated expression of ET-1 . Co-culture models revealed the essential role of BMP9-mediated PMVEC paracrine signaling in modulating PASMC contractile phenotype markers ( CNN1 ; TAGLN ), which was attenuated by anti-CXCL12, CXCR4 antagonist, or anti-BMP9. Conclusions: BMP9 is a central regulator of vasoactive endothelial genes via ALK1-SMAD3 signaling that modulate PASMC phenotype and contribute to experimental PH.

This study revealed the prevalence of paracentral scotoma in highly myopic eyes with early open angle glaucoma, and highlighted structural and vascular parameters associated with paracentral scotoma, which may facilitate the assessment of central visual function. To investigate the prevalence and associated factors of paracentral scotoma in patients with high myopia and early open angle glaucoma (OAG). In this cross-sectional study, myopic eyes with early OAG (mean deviation of visual field > -6dB) were categorized into the high myopia group and the low-to-moderate myopia group. Paracentral scotoma was defined as a visual field defect in one hemifield within 10 degrees of fixation. The prevalence of paracentral scotoma was compared between the 2 groups. Association between structural and vascular factors and paracentral scotoma was investigated by logistic regression analysis. A total of 220 myopic eyes with early OAG were enrolled, including 136 highly myopic eyes, and 84 low-to-moderate myopic eyes. Paracentral scotoma was more prevalent in the high myopia group (39.7% vs. 22.6%, P = 0.012). Multivariate logistic regression analysis showed that thinner circumpapillary retinal nerve fiber layer (cpRNFL) thickness in inferior-temporal and temporal-upper sectors, thinner inferior ganglion cell complex (GCC) thickness, lower radial peripapillary capillary (RPC) vessel density in inferior-temporal and temporal-lower sectors, and lower inferior perifoveal vessel density were significantly associated with paracentral scotoma in highly myopic eyes with early OAG (all P < 0.05). Compared with low-to-moderate myopia, highly myopic eyes with early OAG were more likely to develop paracentral scotoma. The measurement of cpRNFL thickness and RPC vessel density in the temporal and inferior-temporal sectors, GCC thickness, and perifoveal vessel density in the inferior sector may help assessment of central visual function in highly myopic eyes with early OAG.

Slit2-robo signaling regulates angiogenesis and repair following myocardial infarction.

Understanding late-onset neurological deficit in severe rigid Scoliosis: A comprehensive review.

SNHG16-loaded extracellular vesicles from hypoxic NSCLC cells drive M2 macrophage polarization to enhance cancer aggressiveness.

Addressing sexual difficulties in Parkinson's disease.

ABSTRACTTraumatic brain injury (TBI)—a serious brain damage caused by accidents, falls, and sports—causes vasogenic edema, neuroinflammation, and neurological dysfunction resulting from blood–brain barrier disruption. Sonic hedgehog (Shh), a secretory protein belonging to the hedgehog family, protects cerebrovascular and neuronal function via the patched‐1 (Ptch‐1)–smoothened (Smo)–Gli pathway. In this study, we investigated the effects of Smo agonists (Shh and SAG) and antagonist (Jervine) on vasogenic edema, neuroinflammation, and neurological dysfunction in mice following TBI. Male ddy mice (8 weeks old) were used to minimize the influence of gonadal hormones on the results. A TBI model was established by inflicting a fluid percussion injury (FPI) on mouse cerebrum or cultured cells. Shh expression increased in mouse cerebrums and cultured astrocytes after FPI. Vasogenic edema was assessed by Evans blue extravasation into brain tissue and increased brain water content. Evans blue extravasation and brain water content increased after FPI. Repeated intracerebroventricular administration of recombinant Shh reduced Evans blue extravasation and brain water content in the cerebrum after FPI, whereas treatment with Jervine, an Smo antagonist, aggravated these conditions. Recombinant Shh administration also decreased the expression of inflammatory cytokines and chemokines in the cerebrum after FPI. Notably, repeated intravenous administration of SAG, a small‐molecule Smo agonist, reduced FPI‐induced vasogenic edema and neuroinflammation, and improved neurological dysfunction in mice. Furthermore, SAG treatment increased the expression of vascular protective factors and tight junction proteins. These results suggest that Smo agonists are promising therapeutic agents for TBI.

The purpose of the study In the context of demographic aging, the development of individualized rehabilitation programs for elderly patients has become a key area of focus. Vascular factors that affect mobility, cognitive status, and the risk of complications have gained particular importance. Objectives. Based on the ultrasound assessment of the lower extremity arteries, determine the differences in vascular parameters in patients with cognitive, motor, and mixed rehabilitation profiles, and justify their significance for building rehabilitation treatment programs. Material and methods. 96 patients of older age groups (mean age 78.4 ± 6.7 years) living in a long-term care hospital were examined. Duplex scanning of the main arteries below the inguinal fold was performed, and the indicators of stenosis, systolic blood flow velocity, and pulsation index were calculated. The patients were divided into three rehabilitation profiles: cognitive (n=34), motor (n=30), and mixed (n=32). Results. Patients with an motor profile showed the most pronounced multilevel stenoses (up to 52 % in the common femoral artery and 43 % in the popliteal artery), a decrease in blood flow velocity, and an increase in the pulsation index, which reflects high peripheral resistance and the risk of trophic disorders. In the cognitive group, vascular changes were significantly less pronounced, which is associated with better perfusion indicators. In patients with a mixed profile, the results were intermediate, demonstrating the combined influence of cognitive and motor factors. Conclusion. Vascular indicators increase the accuracy of determining the clinical and rehabilitation profile and should be taken into account when creating individual programs for older age groups. Ultrasound assessment of the lower extremity arteries allows for objective stratification, prediction of complication risks, and determination of the direction of physiotherapeutic interventions.

To compare the visual task-evoked microvascular response in the macula between normal-tension glaucoma (NTG) and high-tension primary open-angle glaucoma [i.e., high-tension glaucoma (HTG)] by using optical coherence tomography angiography (OCTA). In this case-control observational study, ten eyes of 10 patients with HTG, twelve eyes of 12 patients with NTG and eleven eyes of 11 healthy participants were included. All glaucoma eyes had a preserved central visual field of at least 10° and best corrected visual acuity of 20/40 or better. Macular superficial vessel density (VD) was measured by OCTA at baseline and then immediately after a 12.5Hz white light flicker stimulation. Flicker light stimulation evoked significant increase in macular superficial VD of HTG (baseline vs. poststimulation:35.31% ± 4.31% vs. 36.07% ± 4.35%, P = 0.048) and control eyes (46.21% ± 2.94% vs. 47.09% ± 2.68%, P = 0.028) but not the eyes with NTG (37.98% ± 5.99% vs. 37.44% ± 5.69%, P = 0.622). The absolute change in VD (ΔVD) was significantly smaller in NTG eyes compared to control eyes (-0.54% ± 1.40% vs. 0.88% ± 1.14%, P = 0.026). NTG eyes also had a lower VD change percentage in the temporal macula than that in HTG eyes (-1.17% ± 5.53% vs. 4.01% ± 4.73%, P = 0.042). Visual task-evoked vasoreactivity changes provide additional information in the understanding and assessment of the pathophysiological mechanisms of glaucoma. Discrepancies in the retinal vasoreactivity between HTG and NTG imply that vascular factors may play different roles in the onset and progression of these diseases. What isknown Vessel density (VD) of the macular superficial retina has been proven to be reduced in individuals suffering from primary open-angle glaucoma (POAG). The reduction of VD has been found to be correlated with the progressive development of glaucoma. What isnew Patients with normal-tension glaucoma (NTG) has impaired vasoreactivity to visual stimulation compared with high-tension POAG. The visual stimulation-assisted dynamic optical coherence tomography angiography (OCTA) technique can provide additional information for the vascular dysregulation in the pathophysiology of subtypes of POAG.

Spinal deformity surgery carries a high risk of intraoperative neuromonitoring (IONM) signal loss and neurological complications. The Cobb angle has traditionally been used to assess spinal deformity severity, but the Deformity Angular Ratio (DAR) has been proposed as a potentially more precise predictor of surgical risks. This systematic review and meta-analysis aimed to compare the preoperative DAR to the Cobb angle to predict the loss of IONM signal and the presence of postoperative neurological complications in spinal deformity correction. A systematic literature search followed PRISMA guidelines across PubMed, Scopus, Embase, and Web of Science from their inception to August 2024. Studies were included if they reported Cobb angles, DAR values, IONM signal loss, and/or neurological complications in spinal deformity patients. The Newcastle-Ottawa Scale (NOS) was used for quality assessment. Random-effects meta-analysis was performed to assess the association between Cobb angles, DAR, IONM signal loss, and neurological complications, with Trim and Fill correction applied to adjust for publication bias. Seven high-quality retrospective cohort studies (1,074 patients) were included. Sagittal Cobb (S-Cobb), Coronal Cobb (C-Cobb), and Total Cobb (T-Cobb) angles were significantly associated with IONM signal loss. Sagittal DAR (S-DAR > 12°) and Total DAR (T-DAR > 22°) were strongly correlated with IONM signal loss, while Coronal DAR (C-DAR) showed no significant association after publication bias correction. T-DAR greater than 39° was the only parameter significantly associated with postoperative neurological complications. DAR demonstrates greater predictive value than the Cobb angle for identifying patients at high risk for IONM signal loss, with T-DAR showing the strongest correlation. The greater impact of sagittal imbalance (S-DAR, S-Cobb) on IONM signal loss is likely due to spinal cord vascular and mechanical factors.

This brief review provides background information about brain health and its definition and public health importance. Within the context of brain health, we focus on two important modifiable cardiovascular risks, obesity and hypertension, and discuss mechanisms by which these factors affect brain health and recent advances in our understanding of trajectories of these risks across the lifespan. Our understanding of obesity, hypertension and brain health has advanced beyond the categorization of these factors as binary (present, absent) variables. The study of trajectories of obesity and hypertension have taught us that the presence of these factors as early as childhood and adolescence may be a signal of brain injury and eventual cognitive impairment as early as one's late 20s or early 30s. Over time each factor may show variability in measures and begin to decline prior to the onset of a clinical diagnosis of cognitive impairment (e.g., 5-10 years earlier). Both obesity and hypertension are key modifiable vascular factors affecting brain health via a complex relationship that exceeds a simple binary association. Primary care clinicians and public health officials are uniquely positioned to influence these factors during periods of susceptibility during the individual lifespan.

Perivascular adipose tissue (PVAT) is a metabolically active, endocrine organ that plays a crucial role in regulating blood vessel tone, endothelial function, vascular smooth muscle cell growth, and proliferation and contributes significantly to the onset and progression of cardiovascular diseases. In a healthy state, PVAT displays anticontractile, anti-inflammatory, and antioxidative properties, which are critical for maintaining vascular homeostasis. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and/or increasing that of pro-contractile factors. In this context, recent studies have identified hydrogen sulfide (H2S) as a key vascular anti-contractile factor released from PVAT. The enzymes responsible for H2S biosynthesis are differentially expressed in PVAT, depending on the vascular bed and species, and their function can be altered by metabolic and cardiovascular diseases. These alterations can influence H2S signalling, further contributing to vascular dysfunction. PVAT-derived H2S may have particular importance in obesity-related vascular disease, hypertension, and diabetes as it has direct paracrine effects on the vasculature. Understanding the role of PVAT-derived H2S in both healthy and diseased states may provide new insights into preventing vascular dysfunction associated with PVAT changes. The dissection of the specific contributions of each enzyme involved in PVAT-derived H2S biosynthesis could be relevant to fully understanding the complex role of H2S in vascular health vs vascular disease. Further research into modulating PVAT-derived H2S provides an exciting avenue to explore novel pharmacological targets against vascular disease pathogenesis.

Light-controlled sequential nanoregulators for antibacterial and anti-inflammatory effects on promoting chronic wound healing.

Background/Objectives: The variability in the structure of the deep cerebral venous system in neonates is increasingly recognised, as are the vascular structural factors involved in the development of the germinal matrix/intraventricular haemorrhage (GM/IVH) in premature infants. We aimed to characterise the ultrasound patterns of these veins in different categories of newborns and to assess if there is a correlation between certain patterns and angles and the presence of GM/IVH. Methods: One hundred neonates (68 at-term and 32 preterm) were included in this research. The pattern of venous drainage and the angle at the confluence between the terminal vein (TV) and internal cerebral vein (ICV) were identified on coronal sections through the anterior fontanel. The normal pattern was considered as that in which the confluence between the TV and the ICV could be identified, and the atypical pattern was considered the situation in which no confluence or terminal vein was identified. Results: There was no statistically significant difference regarding the normal or atypical venous patterns between the groups (p < 0.443), neither regarding the angles between TV and ICV between term and preterm neonates (p < 0.279—left; p < 0.718—right), and singletons and twins (p < 0.745 left; p < 0.418 right), or between the angles on the left and on the right in the whole group (p < 0.121 and the subgroups of term (p < 0.440) and preterm neonates (p < 0.092). The mean value of the angle at the confluence between the TV and the ICV on the left, was significantly lower in the premature infants with GM/IVH (124.90° vs. 137.02°; p = 0.012), being a good predictor for the occurrence of the lesion (AUC = 0.793; IC 95%: 0.580–1.006; p = 0.018), with a sensitivity of 79%, a specificity of 67%, and a cut-off value of 126.90°. In patients with GM/IVH, the angle was significantly lower on the side with the haemorrhage than on the side without haemorrhage (p < 0.043). Conclusions: There is no difference in the central venous pattern or angle at the confluence of the TV and the ICV between different categories of neonates. The angle at the confluence between the TV and ICV could identify the cases at risk for GM/IVH as well as the side of occurrence of the haemorrhage, offering the opportunity of developing personalised prevention strategies. The lack of an MRI comparator of these measurements limits the practical importance of this study.

Vessel-lining endothelial cells (ECs) rely on heparan sulfate (HS) proteoglycans to regulate vascular permeability and to maintain vascular homeostasis. Hpa2 (heparanase 2) is a little-known, nonenzymatic, HS-binding protein. We hypothesized major functions and thus characterized the role of endogenous Hpa2 in the vertebrate vascular system. We use zebrafish larvae as our primary animal model. Hpa2 loss-of-function (LOF) was induced by CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) and morpholino antisense strategies. We assessed vascular permeability, blood vessel architecture, and EC morphology using transgenic zebrafish and transmission electron microscopy. rHpa2 (recombinant heparanase 2) was generated to study the functionality of Hpa2 in endothelial tissue cultures, zebrafish, and mice. We detected Hpa2 expression in hepatic tissue and localized Hpa2 protein in the vasculature of zebrafish and mammals. Hpa2 LOF increased zebrafish vascular permeability and altered EC and extracellular matrix morphology. rHpa2 rescued the Hpa2 LOF phenotype. Hpa2 LOF reduced HS levels and caused EC gene expression changes involved in signal transduction. rHpa2 competed with growth factors FGF2 (fibroblast growth factor-2) and VEGFA165 (vascular endothelial growth factor A165) for binding on the EC surface and consequently reduced the signal response these factors elicit. rHpa2 prevented VEGFA165-induced vascular permeability in murine ex vivo kidneys. Pharmacological inhibition of FGF2/VEGFR (VEGF receptor) signaling alleviated the Hpa2 LOF phenotype in zebrafish. We suggest that Hpa2 is a circulating molecule that maintains vascular integrity by regulating vascular HS-dependent growth factor signaling. Our model outlines Hpa2-related vascular function and could indicate therapeutic utilities.