Search Results (115)

Polycystic ovarian syndrome (PCOS) affects over 116 million women globally and is typically linked with excess androgens such as testosterone. Many patients, however, display classic PCOS symptoms despite normal serum androgen. One proposed mechanism for these cases involves a shortened CAG (i.e., encodes glutamine) repeat length in the androgen receptor (AR) gene, which increases AR activity without elevating testosterone. Fewer glutamine repeats alter the AR’s N-terminal domain and may contribute to strengthened interactions with co-activators and enhanced transcription of androgen-regulated genes. Heightened AR activity in hypothalamus neurons stimulates increased pulsatile release of gonadotropin-releasing hormone (GnRH), which disrupts pituitary secretion dynamics and favors luteinizing hormone (LH) over follicle-stimulating hormone (FSH). This altered LH/FSH ratio leads to impaired folliculogenesis, anovulation and other hallmark PCOS symptoms. Targeting AR activity directly, for example by using compounds that covalently modify the AR N-terminal domain to suppress activity, may therefore offer a more precise treatment strategy for PCOS. Full article

Aortic arch aneurysms are uncommon but clinically significant due to their rapid growth and increasing rupture risk. Analyzing flow changes associated with aneurysm enlargement is essential for understanding mechanisms of disease progression. However, computational studies focusing on the aortic arch aneurysm remain limited. In this study, computational fluid dynamics (CFD) simulations were conducted under pulsatile flow conditions to investigate flow characteristics across different aneurysm sizes. A patient-specific aortic geometry was reconstructed and modified to generate three idealized aneurysm models with diameters of 45, 55, and 65 mm, along with a healthy reference model. Key hemodynamic parameters, including velocity distribution, flow recirculation, wall shear stress (WSS), oscillatory shear index (OSI) and helicity, were analyzed. The results demonstrated that increasing aneurysm size significantly disrupts normal flow patterns, leading to reduced flow velocities and progressively enhanced recirculation zones, particularly during the deceleration phase of the cardiac cycle. Enlarged aneurysms also exhibited consistently low WSS, elevated OSI, and disrupted helical flow patterns along the vessel walls. These adverse hemodynamic conditions are associated with intraluminal thrombus (ILT) formation, localized wall thinning, and increased risk of dissection or rupture. Overall, this study highlights the critical role of aneurysm size in shaping aortic arch hemodynamics and provides a computational framework for assessing disease progression and rupture potential. Full article

Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder with high morbidity and mortality, despite advances in aneurysm securing and neurocritical care. Clinical outcomes are determined by early brain injury (EBI), delayed cerebral ischemia (DCI), hydrocephalus, and long-term cognitive impairment, extending beyond the traditional focus on large-vessel vasospasm alone. Emerging evidence identifies the dysfunction of the glymphatic system and meningeal lymphatic pathway, the brain’s primary clearance pathways, as a central and unifying mechanism linking acute hemorrhagic injury to delayed and chronic neurological sequelae. Following SAH, acute intracranial pressure elevation, subarachnoid blood clot burden, loss of arterial pulsatility, venous congestion, astrocytic aquaporin-4 perivascular depolarization, and neuroinflammation converge to suppress cerebrospinal fluid–interstitial fluid exchange and outflow in glymphatic system and subsequent meningeal lymphatic drainage. Persistent clearance failure promotes the retention of blood breakdown products, inflammatory mediators, and metabolic waste, amplifying microvascular dysfunction, cortical spreading depolarizations, blood–brain barrier disruption, and secondary ischemic injury. Importantly, accumulating data highlight venous pathology and meningeal lymphatic impairment as critical, yet underappreciated, contributors to delayed injury and post-SAH hydrocephalus. In this review, we synthesize the current knowledge of the physiological organization of glymphatic and meningeal lymphatic systems, delineate the mechanistic and molecular drivers of their dysfunction after SAH, and discuss clinical implications for EBI, DCI, hydrocephalus, and long-term cognitive outcomes. We further outline future directions, including translational imaging, biomarker development, and therapeutic strategies targeting clearance pathways, to advance disease-modifying approaches in SAH. Full article

The Middle Meningeal Artery (MMA) occupies a pivotal role in the pathophysiology of migraine, functioning as a vascular and neuroimmune interface that precipitates the characteristic pulsatile pain. The inhibition of this pathophysiological cascade has been investigated as a therapeutic strategy. However, fewer than a dozen centers globally have disseminated procedural or mechanistic data. Given the nascency of this field and the imperative for standardization, the present review synthesizes mechanistic and clinical evidence underpinning intra-arterial pharmacological modulation of the MMA for migraine management. Methods: A focused narrative review was undertaken, drawing upon select but influential studies from pioneering research groups investigating intra-arterial interventions targeting the MMA. The extant literature was thematically categorized and organized according to the loci of cascade interruption and their corresponding clinical outcomes. Results: Since 2009, intra-arterial therapies for severe headache syndromes have evolved, initially utilizing nimodipine for vasospasm-related headaches, progressing to verapamil for reversible cerebral vasoconstriction, and more recently, lidocaine for refractory or status migrainosus, occasionally in conjunction with MMA embolization. Contemporary research uses language that conceptualizes migraine as an immunologically mediated neurovascular disorder, as opposed to a purely vascular or neuronal entity. Recent investigations have identified interleukins such as Interleukin-1β, Tumor Necrosis Factor-α, and Interleukin-6 as critical amplifiers of trigeminovascular activation. Purinergic signaling through the P2X3 receptor and the P2Y13 receptor, in conjunction with pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide pathways, has been implicated in the modulation of MMA excitability and neuropeptide release. The development of novel calcitonin gene-related peptide receptor antagonists, such as zavegepant, further substantiates the artery’s significance as a pharmacological target. Conclusions: These findings support a shift toward immune-modulating intra-arterial therapeutic strategies, with migraine interventions targeting cytokine and neuroimmune signaling within the MMA, rather than relying exclusively on vasodilatory mechanisms. Full article

The role of cardiac implantable electronic devices (CIEDs), including implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices, in patients supported with left ventricular assist devices (LVADs) remains controversial. Although ICDs clearly reduce the risk of sudden cardiac death (SCD) and improve outcomes in advanced heart failure (HF), their benefit in patients with continuous-flow mechanical circulatory support is less certain. Initial small studies involving LVAD patients, particularly those with older pulsatile devices, suggested that ICDs confer a survival benefit during LVAD support. However, more recent evidence has been inconsistent. Some studies show modest protection against arrhythmic death, whereas others show no improvement in overall mortality. Similarly, CRT does not appear to offer significant additional hemodynamic benefits after LVAD implantation, and current evidence does not strongly support its routine continuation. Device-related complications—including lead failure, infection, electromagnetic interference, and inappropriate shocks—are major clinical concerns that can offset potential benefits. Accordingly, current guidelines recommend maintaining pre-existing ICD or CRT devices in LVAD patients but do not endorse the routine implantation of new devices after LVAD placement. The existing evidence highlights the need for a nuanced and individualized approach to CIED therapy in patients with LVAD. Future research should focus on randomized trials, registry-based analyses, and the exploration of novel technologies such as leadless pacing, subcutaneous ICDs, and advanced programming algorithms. Patient-centered outcomes, particularly quality of life and ethical considerations—such as ICD deactivation in end-of-life scenarios—must be considered in decision-making in this evolving field. Full article

Organ-on-a-Chip (OOC) platforms are microfluidic systems that recreate key features of human organ physiology in vitro via controlled perfusion. Fluid mechanical stimuli strongly influence cell morphology and function, making this important for cardiovascular OOC applications exposed to pulsatile blood flow. However, many existing OOC devices employ relatively simple chamber geometries and steady inflow assumptions, which may cause non-uniform shear exposure to cells, create stagnant regions with prolonged residence time, and overlook the specific effects of pulsatile perfusion. Here, we used computational fluid dynamics (CFD) to investigate how chamber geometry and inflow conditions shape the near-wall flow environment on a cell culture surface at a matched cycle-averaged volumetric flow rate. Numerical results demonstrated that pillarized chambers markedly reduced relative residence time (RRT) versus the flat chamber, and the small pillar configuration produced the most uniform time-averaged wall shear stress (TAWSS) distribution among the tested designs. Phase-resolved analysis further showed that wall shear stress varies with waveform phase, indicating that steady inflow may not capture features of pulsatile perfusion. These findings provide practical guidance for pillar geometries and perfusion conditions to create more controlled and physiologically relevant microenvironments in OOC platforms, thus improving the reliability of cell experimental readouts. Full article

Flexible piezoelectric sensors based on electrospun poly(vinylidene fluoride) (PVDF)/polyacrylonitrile (PAN)/graphene nanofibers were fabricated and evaluated for passive human body motion detection. Optimized electrospinning yielded smooth, continuous fibers with diameters of 200–250 nm and uniform films with thicknesses of 20–25 µm. Fourier transform infrared (FTIR) spectroscopy confirmed a high fraction of the piezoelectrically active β-phase in PVDF, which was further enhanced by post-deposition thermal treatment. Graphene and lithium phosphate were incorporated to improve electrical conductivity, β-phase nucleation, and piezoelectric response, while PAN provided mechanical reinforcement and flexibility. Custom test platforms were developed to simulate low-amplitude mechanical stimuli, including finger bending and pulsatile pressure. Under applied pressures of 40, 80, and 120 mmHg, the sensors generated stable millivolt-level outputs with average peak voltages of 25–30 mV, 53–60 mV, and 80–90 mV, respectively, with good repeatability and an adequate signal-to-noise ratio. These results demonstrate that PVDF/PAN/graphene nanofiber films are promising candidates for flexible, wearable piezoelectric sensors capable of detecting subtle physiological signals, and highlight the critical roles of electrospinning conditions, functional additives, and post-processing treatments in tuning their electromechanical performance. Full article

Microchannels can create disturbed flow patterns by altering pressure gradients, shear forces, and flow symmetry, which are essential in the design of microfluidic devices and, hence, blood-contacting devices. The effect of asymmetric stenosis on pressure, wall shear stress, and velocity in rectangular and circular microchannels with same operating conditions was analyzed in this study using three-dimensional (3D) steady laminar computational fluid dynamics (CFD) simulations. Asymmetric flow patterns induced by asymmetric stenosis are of particular importance and remain underexplored, especially in the context of multiple constrictions. This is, to our knowledge, is the first systematic CFD comparison of multiple asymmetric stenoses in circular microchannels directly contrasted with rectangular and single-stenosis cases under identical settings. Several parameters, such as wall shear stress (WSS), pressure, and velocity distributions, were analyzed in various stenotic and non-stenotic geometries. These microchannel models, while not reflecting real blood vessels themselves nor exhibiting wall compliance, pulsatility, or non-Newtonian rheology, replicate important mechanical characteristics of stenosis-mediated flow disturbance. Single and multiple asymmetric stenoses create flow patterns that are similar to those of vascular pathologies. For this reason, these channels should be considered as simplified device-scale models of vascular phenomena as opposed to realistic, in vitro vascular models. The results showed that asymmetric stenosis creates asymmetric velocity peaks and elevated WSS, which are more evident in the case of circular configurations with double asymmetric stenosis. The findings will help design microfluidic devices that mimic unstable flow characteristics that occur in stenotic conditions, and assist in testing clinical devices. In this study, two fabrication-ready microchannel designs under fixed operating conditions (identical inlet velocity and fluid properties) that reflect common microfluidic use were compared. Consequently, all pressure, velocity, and WSS outcomes are interpreted as device-scale responses under fixed velocity, rather than a fundamental isolation of cross-section shape, which would require matched hydraulic diameters or flow rates. This study is explicitly device-oriented, representing a fixed operating point rather than a strict geometric isolation. Accordingly, the results are also expressed with dimensionless loss coefficients (Ktot and Klocal) to enable scale-independent, device-level comparison. Full article

Objective: To evaluate hepatic artery Doppler parameters in fetuses with fetal growth restriction (FGR) and to investigate their relationship with composite adverse neonatal outcomes (CANO). Methods: This prospective cohort study included 108 pregnancies (54 FGR; 54 appropriate-for-gestational-age controls) between 34 and 37 weeks’ gestation. Hepatic artery (HA), umbilical artery (UA), middle cerebral artery (MCA), and uterine artery Doppler indices were recorded. Logistic regression and ROC analyses were used to determine predictors of FGR and CANO. Results: HA pulsatility index (PI), systolic/diastolic ratio, and peak systolic velocity (PSV) were significantly higher in FGR fetuses (p < 0.05). In multivariate regression, HA-PI remained independently associated with FGR (aOR 1.74, 95% CI 1.07–2.87, p = 0.025). For predicting CANO, HA-PSV was the only independent predictor (aOR 1.05, 95% CI 1.00–1.10, p = 0.020). ROC analysis demonstrated moderate discriminative ability for HA-PI (AUC 0.681) and HA-PSV (AUC 0.703). Conclusions: Increased HA-PSV in FGR reflects activation of the hepatic arterial buffer response as an adaptive mechanism to maintain hepatic perfusion under hypoxic stress, whereas elevated HA-PI may represent evolving microvascular resistance. Hepatic artery Doppler evaluation may serve as a complementary tool for assessing fetal well-being and identifying fetuses at risk for adverse neonatal outcomes, particularly in late-onset FGR. Full article

Background and Objectives: Blood flow is critical for tissue oxygenation, and alterations in cerebrovascular and peripheral circulation have important health implications. This study aimed to examine the impact of distinct mechanisms for increasing intra-cavity pressure through the abdominal bracing (AB) and Valsalva maneuver (VM) on central and peripheral hemodynamics. Materials and Methods: A randomized crossover design was used, and thirty healthy young adults (age 21.9 ± 1.5 years; BMI 20.9 ± 1.8 kg/m²) performed AB and VM in a randomized order. All participants provided written informed consent, and the study protocol was approved by the Clinical Research Information Service (KCT0009742; registered on 30 August 2024). Hemodynamic responses were measured before and after each intervention, including heart rate, blood pressure, pulse wave velocity, carotid artery diameter, pulsatility index, resistive index, peripheral oxygen saturation, and cerebral oxygenation. Repeated-measures analysis of variance and paired t-tests were conducted on the datasets. Results: Both the VM and AB significantly increased heart rate (p < 0.001) and systolic blood pressure (VM: p = 0.015; AB: p < 0.001). Cerebral oxygen saturation decreased significantly (VM: p < 0.05; AB: p < 0.05), whereas oxyhemoglobin increased during both interventions, suggesting higher cerebral oxygen demand. The VM specifically increased the carotid pulsatility index (pre = 1.76 ± 0.28; post2 = 1.87 ± 0.33; p = 0.008), reflecting elevated central vascular resistance. In contrast, AB decreased peripheral oxygen saturation (pre = 98.43 ± 0.71; post1 = 97.49 ± 1.76; p < 0.001) and increased peripheral (heart–finger) pulse wave velocity (Lt: p = 0.026; Rt: p = 0.010), indicating greater stimulation of peripheral circulation. Conclusions: Distinct mechanisms that elevate intra-cavity pressure differentially influence central and peripheral hemodynamics. These findings suggest that intra-cavity pressure can selectively modulate hemodynamic responses, with potential applications in both clinical and exercise settings. Full article

Measuring RBC aggregation can be considered as a valuable tool for detecting pathological diseases. Most previous methods need to stop and run blood flows periodically. Thus, it is impossible to probe RBC aggregation in continuously varying infusion flow. To resolve the issues, a novel bifurcated continuous-flow mechanism is suggested to probe RBC aggregation without periodic interruption of blood flow. A microfluidic chip is then designed to split single flow into two branches (low flow rate and high flow rate). RBC aggregation occurs in the low flow-rate channel, whereas it is dispersed fully in the high flow-rate channel. Using a syringe pump, blood is infused into a microfluidic chip at constant and sinusoidal pattern. RBC aggregation index (AI) is calculated from time-lapse imaging intensity within each channel. From fluidic circuit analysis and experimental results, the optimal infusion flow rate is determined as Q_sp = 0.5~2 mL/h. The AI is higher at Hct = 30% than at Hct = 50%. The high concentration of dextran solution increases AI considerably. The period of pulsatile infusion flow rate has a strong influence on time-lapse AI. In conclusion, the present method can be capable of measuring time-lapse AI consistently, without interrupting infusion flow. Full article

Intact regulation of cerebral blood flow (CBF) is essential for preserving cognitive function and reducing the risk of cerebrovascular events, particularly in the aging population. Autoregulation of CBF is one of the fundamental mechanisms that ensure constant supply for brain tissue by maintaining relatively stable perfusion despite fluctuations in systemic blood pressure. It also acts as a critical protective mechanism, shielding the fragile cerebral microcirculation from potentially harmful pressure fluctuations and hence excessive pulsatility. The loss or attenuation of this protective mechanism with aging or disease increases the vulnerability of the microvasculature to structural damage, blood–brain barrier (BBB) disruption, and the development of cerebral small vessel disease. This mini-review summarizes current understanding of how aging affects cerebral autoregulation, highlighting underlying mechanisms, clinical consequences, and potential strategies to preserve cerebrovascular health in older adults. Full article

Background: The fetal mechanical PR interval (mPR), measured using pulsed-wave Doppler, is a widely used parameter to assess atrioventricular conduction in fetuses, particularly in cases at risk of developing atrioventricular (AV) block. However, the physiological factors that influence mPR readings are not fully understood. This study aimed to identify determinants affecting the measurement of the mPR interval using the mitral valve/aorta (MV/Ao) Doppler method in a cohort of structurally normal fetuses. Methods: We retrospectively analyzed 925 fetuses with normal echocardiographic findings and no structural cardiac or extracardiac anomalies. Correlation analysis, group comparisons, trend testing, and multivariable modeling were performed to assess the impact of biometric and Doppler parameters on mPR interval measurements. Results: The median mPR interval across the cohort was 116 ms (interquartile range: 108–123 ms). Fetuses were categorized into four gestational age groups (≤19 weeks, 20–23 weeks, 24–27 weeks, and ≥28 weeks). Significant differences in mPR were observed between gestational age groups (p < 0.01), with a positive trend across increasing gestational age (p < 0.0001). The strongest correlation was an inverse relationship between mPR and fetal heart rate (FHR) (ρ = −0.256, p < 0.01). Multivariable regression identified five independent predictors of mPR: lower FHR, greater biparietal diameter (BPD), larger pulmonary valve diameter (PVD), increased fronto-occipital diameter (FOD), and lower umbilical artery pulsatility index (UA PI). The final model explained approximately 9.9% of the variance in mPR interval (R² = 0.099). Conclusions: The fetal mPR interval increases with gestational age and is primarily influenced by fetal heart rate, even after adjusting for other factors. Certain biometric and Doppler parameters also contribute modestly to mPR variation. These findings highlight the importance of accounting for physiological variability when interpreting mPR measurements in clinical fetal cardiology. Full article

In this review we propose the hypothesis that an energy-dissipating process precedes the continuous stimulation of insulin secretion by glucose. This process is mediated by connexin 36 hemichannels (Cx36H), or Cx36 connexons. Cx36H oligomers are expressed at the plasma membrane, and their gating activity (opening) is activated by plasma membrane depolarization after the closure of K⁺ATP channels by glucose (>5 mM) metabolism. This initial depolarization (1st step) might be responsible for the first phase of insulin secretion, with the subsequent opening of Cx36H increasing β-cell plasma membrane permeability, allowing for the efflux of metabolites (less than 1KD) (GABA, adenine nucleotides) and K⁺ (2nd step). This provokes a breakdown of oxidative glucose metabolism and the repolarization of the plasma membrane. As the extracellular glucose concentration increases further (>>5 mM), it exerts a progressive inhibition effect on Cx36H opening, allowing for the continuous stimulation of insulin secretion (3d step, second phase,). The glucose feature of regulating Cx36H closing with sigmoidal kinetics (8 mM IC₅₀ and around 20 mM at maximum) has been confirmed in mouse Cx36 connexin expression in Xenopus oocytes and in mouse islets stimulated by a range of glucose concentrations in the presence of 70 mM KCl. This gating activity was also inhibited by some non-metabolized glucose analogs. Glucose inhibition of Cx3H opening might not only contribute to making the insulin secretory response more specific for glucose but might also play a role in the pulsatility of sustained insulin secretion. Cx36H opening also offers the opportunity to potentiate the secretory effect in vivo by, permeant or not, metabolic stimuli. Confirmation of this novel physiological role for Cx36H in β-cells would place them as new susceptibility locus for type 1 and type 2 diabetes, whose physiological implication in the mechanism of insulin secretion regulation should be evaluated by in vivo studies in diabetic patients. Full article

Major depressive disorder (MDD) is a prevalent and disabling condition. Transcranial direct current stimulation (tDCS) may improve symptoms by modulating neuroplastic and inflammatory mechanisms. This randomized, double-blind, placebo-controlled trial will recruit adult outpatients with MDD showing residual symptoms despite at least four weeks of stable SSRI treatment. Participants will be randomized to active or sham add-on tDCS while continuing their antidepressant regimen. The intervention will consist of 15 sessions over 3 weeks, targeting the left dorsolateral prefrontal cortex (anode F3, cathode F4) at 2 mA for 30 min per session. The primary outcome is the reduction of depressive symptoms measured by the Hamilton Depression Rating Scale-17 (HDRS), with remission defined as HDRS-17 ≤ 7. Secondary outcomes include cognitive performance (attention, executive functioning, memory), serum biomarkers (BDNF, VEGF, NGF, NRG1, angiogenin, IGF1, IL-6, TNF-α), cortical excitability assessed by transcranial magnetic stimulation (motor threshold, silent period, intracortical inhibition/facilitation), and cerebral hemodynamics by transcranial Doppler sonography (blood flow velocity, pulsatility, resistivity). Assessments will occur at baseline, post-treatment, and 3- and 6-month follow-ups. This trial aims to evaluate the efficacy of adjunctive tDCS in MDD with residual symptoms and its biological correlates, bridging clinical improvement with electrophysiological and neurovascular mechanisms. Full article