Systemic Circulation Research Articles

Rapid estimation of left ventricular contractility with a physics-informed neural network inverse modeling approach

Physics-based computer models based on numerical solutions of the governing equations generally cannot make rapid predictions, which in turn limits their applications in the clinic. To address this issue, we developed a physics-informed neural network (PINN) model that encodes the physics of a closed-loop blood circulation system embedding a left ventricle (LV). The PINN model is trained to satisfy a system of ordinary differential equations (ODEs) associated with a lumped parameter description of the circulatory system. The model predictions have a maximum error of less than 5% when compared to those obtained by solving the ODEs numerically. An inverse modeling approach using the PINN model is also developed to rapidly estimate model parameters (in ∼ 3 min) from single-beat LV pressure and volume waveforms. Using synthetic LV pressure and volume waveforms generated by the PINN model with different model parameter values, we show that the inverse modeling approach can recover the corresponding ground truth values for LV contractility indexed by the end-systolic elastance Ees with a 1% error, which suggests that this parameter is unique. The PINN inverse modeling approach is then applied to estimate Ees using waveforms acquired from 11 swine models, including waveforms acquired before and after administration of dobutamine (an inotropic agent) in 3 animals. The estimated Ees is about 58% to 284% higher for the data associated with dobutamine compared to those without, which implies that this approach can be used to estimate LV contractility using single-beat measurements. The PINN inverse modeling can potentially be used in the clinic to simultaneously estimate LV contractility and other physiological parameters from single-beat measurements.

Early coronary artery atherosclerosis in humans is associated with attenuated coronary retention of klotho

Abstract Background Vascular aging is a key feature of cardiovascular disease. α-klotho (klotho) is a protein inversely associated with aging and may contribute to vascular repair. Lower levels of systemic klotho have been identified in humans with features of early and advanced coronary atherosclerosis. It remains unknown if circulating klotho is present within human coronary circulation and whether cardiovascular klotho retention correlates with atherosclerosis. Purpose The current study aimed to assess the presence of klotho within coronary circulation compared to systemic circulation and hypothesized that net coronary klotho retention is attenuated in patients with early age-related features of coronary artery disease (CAD). Methods A total of 42 patients that underwent clinically indicated coronary angiogram for chest pain that had no obstructive CAD underwent intravascular ultrasound (IVUS) assessment were retrospectively examined. Virtual histology assessed coronary plaque characteristics. Blood samples simultaneously collected from the proximal aorta and coronary sinus were used for klotho detection using enzyme-linked immunosorbent assay. The net gradient of klotho across cardiovascular circulation was calculated by multiplying the arteriovenous klotho gradient by basal coronary blood flow. A net positive gradient indicated less cardiovascular klotho retention; a net negative gradient indicated greater cardiovascular klotho retention. Results Overall, participants were age 54±10 years old and 76% were female. There were overall higher levels of klotho within the coronary sinus (median 0.49 ng/mL [0.15; 1.69]) compared to systemic circulation (median 0.30 ng/mL [0.16; 1.14]). Participant groups were determined by those with positive (n = 20) or negative (n = 22) cardiovascular retention of klotho. Both groups were similar in age (56 ±2 vs. 51 ±2 years old, p = 0.080), gender (72% vs. 80% female, p = 0.580), and had similar occurrences of traditional cardiovascular comorbidities. Those with less cardiovascular klotho retention in the coronary vascular bed had significantly greater degree of non-obstructive coronary artery plaque (Gensini score 3.5 vs. 0, p < 0.001) and had higher percent plaque burden (46% [35; 53] vs. 34% [28; 46], p = 0.044) than those with greater cardiovascular klotho retention. Conclusions Patients with early coronary atherosclerosis may be characterized by attenuated retention of klotho within coronary circulation. Moreover, humans appear to have higher circulating klotho in coronary circulation than in systemic circulation. The current study may support a role for mechanism or potential therapeutic target for klotho in coronary atherosclerosis in humans.

Toxicokinetics and Tissue Distribution of the Hepatotoxic Triterpenoid Saponin Pterocephin A in Rats Using the Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) Method

Pterocephin A is a natural triterpenoid saponin isolated from Pterocephalus hookeri, a traditional Tibetan medicine with slight toxicity, which can induce liver injury in rats. This study aimed to establish a sensitive and reliable UPLC-MS/MS method for exploring the toxicokinetics and tissue distribution of pterocephin A following single intravenous and intragastric administration. Pterocephin A and prosapogenin 1C (internal standard, IS) were extracted using a simple protein precipitation technique with methanol as the precipitant for plasma samples and methanol/acetonitrile = 1:1 (v/v) for tissue samples. UPLC separation was achieved by gradient elution with 0.3 mL/min and a mobile phase consisting of 5 mM ammonium formate (A) and acetonitrile (B) (0–2 min 30% B; 2–4 min: 30–80% B; 4–5 min: 80–98% B; 5–6.5 min: 98% B; 6.5–7 min: 98–30% B; and 7–8 min: 30% B, v/v) with a column temperature of 35 °C. MS spectrometry adopted negative ion scanning mode, primary MS spectrometry adopted full scan monitoring mode, and secondary MS spectrometry adopted targeted MS2 scan monitoring mode. The assay exhibited a linear dynamic range of 0.02–15 μg/mL for pterocephin A in biological samples, with the low limit of quantification set at 0.02 μg/mL. Non-compartmental toxicokinetic parameters indicated that pterocephin A was well absorbed into the systemic circulation and had a long residual time after intravenous (10 mg/kg) and intragastric (60 mg/kg) administration, as it could still be detected after 72 h. Tissue distribution analysis revealed detectable levels of pterocephin A in various tissues, and a high concentration was maintained in the liver after intravenous (10 mg/kg) administration, with the highest concentration being 610.95 ± 25.73 ng/mL and a specific distribution pattern of liver > lung > kidney > intestine > spleen > testes > heart > stomach. The toxicokinetic process and tissue distribution characteristics of pterocephin A were expounded in this study, which can provide relevant data support for further research and clinical application of pterocephin A with its slight toxicity.

Treatment of chronic sinus tract leakage at rectal anastomosis with anal fistula endoscopy

Objective: To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site. Methods: We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube. Results: The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery. Conclusion: Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.

Candida albicans Induces Oral Microbial Dysbiosis and Promotes Oral Diseases

Candida albicans are ubiquitous fungal organisms that colonize the oral cavity of healthy individuals without causing disease. C. albicans is an opportunistic microorganism with several virulent factors that influence the inflammatory process and allow it to invade tissues, evade host defense mechanisms, and release toxins, facilitating proliferation and degradation. At present, increasing emphasis is placed on polymicrobial interactions between C. albicans and various bacterial pathogens. Such interaction is mutually beneficial for both parties: it is competitive and antagonistic. Their complex interaction and colonization in the oral cavity serve as the basis for several oral diseases. The dispersion of C. albicans in saliva and the systemic circulation is noted in association with other bacterial populations, suggesting their virulence in causing disease. Hence, it is necessary to understand fungal–bacterial interactions for early detection and the development of novel therapeutic strategies to treat oral diseases. In this paper, we review the mutualistic interaction of C. albicans in oral biofilm formation and polymicrobial interactions in oral diseases. In addition, C. albicans virulence in causing biofilm-related oral diseases and its presence in saliva are discussed.

Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.

Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance. To tackle these issues, we developed MA-loaded dissolving microneedles (MA-MNs) with significantly improved bioavailability for osteoporosis therapy. We investigated the influence of drug loading on the physicochemical properties, transdermal permeation behavior, and pharmacokinetics of MA-MNs. The drug loading of MA-MNs exerted almost no effect on their morphology, mechanical property, and skin insertion ability, but it compromised the transdermal permeability and bioavailability of MA-MNs. Compared with oral MA, MA-MNs with the lowest drug loading (224.9μg/patch) showed a 9-fold and 25.8-fold increase in peak concentration and bioavailability, respectively. This may be ascribed to the reason that the increased drug loading can generate higher burst release, higher drug residual rate, and drug supersaturation effect in skin tissues, eventually limiting drug absorption into the systemic circulation. Moreover, MA-MNs prolonged the half-life of MA and provided more steady plasma drug concentrations than intravenously injected MA, which helps to reduce dosing frequency and side effects. Therefore, dissolving MNs with optimized drug loading provides a promising alternative for bisphosphonate drug delivery.

Metabolic Effects of Medium-Chain Triacylglycerol Consumption are Preserved in Obesity.

Several health beneficial effects are associated with intake of medium-chain triacylglycerol (MCT), however, the underlying mechanisms are unknown. Furthermore, it remains uncertain whether the acute metabolic effects of MCT differ between lean individuals and individuals with obesity - and whether these effects are sustained following chronic intake. This study aimed to elucidate the postprandial physiological and metabolic effects of MCT before and after eight days intake compared to intake of energy-matched triacylglycerol consisting of long-chain fatty acids (LCT) using a randomized cross-over design in lean individuals (n=8) and individuals with obesity (n=8). The study revealed that consumption of MCT increased ketogenesis and metabolic rate, while lowering blood glucose levels over five hours. The hypoglycemic action of MCT intake was accompanied by a concomitant transient increase in plasma insulin and glucagon levels. Interestingly, the effects on ketogenesis, metabolic rate, and glycemia were preserved in individuals with obesity and sustained after eight days of daily supplementation. Lipidomic plasma analysis in lean individuals (n=4) showed that a part of the ingested MCT bypasses the liver and entered the systemic circulation as medium-chain fatty acids (MCFA). The findings suggest that MCFA, along with ketone bodies from the liver, may act as signaling molecules and/or substrates in the peripheral tissues, thereby contributing to the effects of MCT intake. In summary, these findings underscore the health benefits of MCT in metabolically compromised individuals after daily supplementation. Moreover, we uncover novel aspects of MCFA biology, providing insights into how these fatty acids orchestrate physiological effects in humans.

Assessment of metabolic indicators of the cardiovascular system in children with nephrotic syndrome

Objective: to evaluate the metabolic parameters of the cardiovascular system in nephrotic syndrome in children Material and methods: 110 children hospitalized with nephrotic syndrome in the nephrology department of the Samarkand Regional Children’s Multidisciplinary Medical Center were examined. Results: Renocardial syndrome with nephrotic syndrome develops in 64.8% of cases, the majority of patients are children 3-6 years of age (44.1%), with a predominance of boys (58.8%). In a cardiometric study in patients with nephrotic syndrome, renocardial syndrome is manifested by significant changes in metabolic and adaptation parameters: oxygen and lactate content - by 1.5 times, creatine phosphate - by 20%, tension index - by 4.8 times and vascular stiffness index - by 5.2 times. Conclusion: Deviation of cardiometry indicators in different age groups indicates a decrease in the intensity of blood circulation in organs and systems, indicating a significant load on the cardiovascular system in nephrotic syndrome.

Appraisal of partial anomalous pulmonary venous drainage through a lumped-parameter mathematical model: a new pathophysiological proof of concept.

Haemodynamic determinants of the ratio between pulmonary and systemic flow (Qp/Qs) in partial anomalous pulmonary venous return (PAPVR) are still not fully understood. Indeed, among patients with the same number of lung segments draining anomalously, a great variability is observed in terms of right ventricular overload. The aim of this study was to test the hypothesis that the anatomic site of drainage, affecting the total circuit impedance, independently influences the magnitude of shunt estimated by Qp/Qs. A zero-dimensional (0D) lumped parameter mathematical model was developed and validated on a sample of patients. We developed a 0D lumped parameter model, using time varying elastances for heart chambers, RLC Windkessel circuits for the systemic and pulmonary circulations. Patients, were categorized into vena cava (VC) type (including left drainage to anomimous vein) and right atrium type (RA). The mathematical model is a system of ordinary differential equations that are numerically solved by means of the ode15s solver in the Matlab environment. The model showed an increase of Qp/Qs with the increase of the number of anomalous veins. With the same number of anomalous veins, Qp/Qs was lower in patients with anomalous drainage to the vena cava (VC) as compared with right atrium (RA) The validation sample consisted of 49 patients (27, 55% females). As predicted by the model, patients with PAPVR with VC type displayed a lower invasive and CMR Qp/Qs as compared with drainage to RA: 1.4 (1.2-1.7) and 1.45 (1.25-1.6) versus 2 (1.75-2.1) and 1.9 (1.6-2) p < 0.05. After stratifying for number of lung territories a lower Qp/Qs was measured in patients with VC PAPVR as compared with RA. In patients with PAPVR, the site of anomalous drainage modulates the Qp/Qs. According to the model, this effect is mediated by the post-capillary impedance of the circuit and significantly decreases with the increase of pulmonary vascular resistances.

Research on New Spatial Data Infrastructure Supports the Circulation of Geographic Information Data Elements

Abstract. Data is an important factor of production in the digital economy era and an important support for building a new development pattern. As an important part of data resources, geographic information data is also an important new factor of production, which plays a unique role in the construction of digital China and economic and social development. From the perspective of releasing the value of data elements, data infrastructure is a new type of infrastructure that provides integrated data aggregation, processing,circulation, application, operation, and security services for society under the support of network, computing power and other facilities. It is an organic whole covering hardware, software, open source protocols, standards, and mechanism design. Spatial data infrastructure (SDI) is a collection of technologies, policies and systems that realize the access and access of spatial data. Through the construction of new spatial data infrastructure (NSDI), it supports the circulation of geographic information data elements,making it an important part of data infrastructure. Firstly, this paper gives the connotation of geographic information data elements circulation. Secondly, it proposed to construct the circulation system of geographic information data elements on the basis of enumerating and summarizing the spatial data infrastructure, in order to better support the construction of digital China and economic and social development. Thirdly, the basic requirements, technical indicators and overall architecture of NSDI are designed. Finally, the opportunities and challenges faced by the circulation of geographic information data elements were summarized, mainly focusing on the aspects of policy mechanisms and security systems. At the end of the paper is a summary and acknowledgments.

Factors Influencing the Central Nervous System (CNS) Distribution of the Ataxia Telangiectasia Mutated and Rad3-Related Inhibitor Elimusertib (BAY1895344): Implications for the Treatment of CNS Tumors.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro-in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited. SIGNIFICANCE STATEMENT: This study examined the disconnect between the in vitro synergy and in vivo efficacy of elimusertib/temozolomide combination therapy by exploring systemic and central nervous system (CNS) distributional pharmacokinetics. Results indicate that the lack of improvement in in vivo efficacy in glioblastoma (GBM) patient-derived xenograft (PDX) models could be attributed to inadequate exposure of pharmacologically active drug concentrations in the CNS. These observations can guide further exploration of elimusertib for the treatment of GBM or other CNS tumors.

Peculiarities of the regional hemodynamics in patients with mono- and bilateral herpes simplex virus stromal keratitis

Background. Herpes simplex virus keratitis (HSVK) is the main cause of blindness in the world resulted from corneal pathology. The blood circulation system of the eye plays an important role in the effective implementation of the immune response. The purpose of the study: to determine the influence of the factor of laterality of the stromal HSVK on the ocular hemodynamics and the frequency of complications. Material and methods. Primary stromal HSVK (was registered for the first time and lasted no more than 3 months) was diagnosed in 32 people (35 eyes), 205 patients (226 eyes) had recurrent stromal HSVK. Among these patients, stromal HSVK was detected both in one eye — unilateral, and in two eyes — bilateral. Complications of stromal HSVK includes: the presence of a transparent graft — in 23 eyes and its opacity — in 10 eyes, secondary glaucoma — in 6 eyes, condition after corneal ulcer — in 16 eyes. The average age of the patients (M ± SD) is 42.2 ± 15.0 years. The control group consisted of 16 healthy volunteers (32 eyes) of similar age. The standard technique of rheoophthalmogram on the ReoCom computer rheograph (Kharkiv, Ukraine) was used. The following indicators were analyzed: rheographic quotient (RQ, ‰) (pulse volumetric blood filling); α1/T (%) — the tone of the large vessels of the eye; velocity of blood filling V (Ohm/s). Results. Patients with stromal HSVK had mainly monolateral eye lesion — 89.8 %, and bilateral lesion was present in 10.2 % of cases. There were no significant differences in the frequency of laterality between primary and recurrent stromal HSVK. In case of recurrence of complicated unilateral and bilateral stromal HSVK, the volumetric pulse blood filling was 17.6 and 30.3 % lower, respectively, than in uncomplicated course, which determines the insufficiency of blood supply to the eye. The rate of blood filling in complicated stromal HSVK was lower than in uncomplicated one by 23 %. At the recurrence of bilateral stromal HSVK, the RQ was higher by 26.4 %, and the rate of blood filling was higher by 36.3 % compared to unilateral one. There were no differences in remission. The tone of the large vessels of the eye with bilateral stromal HSVK is 14 % lower than with unilateral course. Conclusions. In case of recurrent stromal HSVK, the volume pulse blood filling of the eye and its velocity are higher, and the vascular tone is lower than in case of unilateral one, both uncomplicated and complicated. It is assumed that such a significant activation of the ocular hemodynamics is compensatory and contributes to a greater local immune response and improvement of trophism.

Strategies for transportation of peptides across the skin for treatment of multiple diseases.

An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency.

Efficacy of Endovascular Glue Embolization in Treating Ruptured Intracranial Mycotic Aneurysms: A Single Center Experience.

Intracranial mycotic aneurysms (IMAs), rare and often life-threatening, result from arterial wall infections typically caused by bacteria such as Staphylococcus and Streptococcus. The standard treatment for ruptured aneurysms is not well-defined and often individualized. This study investigates the efficacy of endovascular glue embolization in managing ruptured IMAs, based on our center's experience. A retrospective analysis was conducted for ruptured IMAs treated with glue embolization between January 2016 and December 2023. The procedure involved aneurysm sac and parent vessel occlusion with glue delivery. Data included patient demographics, clinical presentations, and neuroimaging. Clinical outcomes were assessed using the modified Rankin scale (mRS) at 3 months, and angiographic follow-up was conducted at 6 months. The study included 28 patients, predominantly male (64.3%), with a mean age of 48 years. Headache was the primary symptom in 92.9% of cases, and positive blood/cerebro spinal fluid cultures were found in 82.14% of cases. All aneurysms were located in the distal circulation, primarily in the anterior circulation system. Glue embolization was successfully performed in all cases, achieving complete aneurysm sac and parent vessel obliteration. Follow-up at 3 months indicated mRS scores of 0 or 1 in 96.5% of cases. Six-month angiographic follow-up showed no aneurysm regrowth or new formations. Endovascular glue embolization demonstrated high efficacy and safety in treating ruptured IMAs, with a 100% obliteration rate and favorable clinical outcomes in this single-center experience. Despite limitations such as its retrospective design and small sample size, the study supports glue embolization as a viable, less invasive alternative to traditional surgery. Further comparative studies are needed to confirm these findings and refine treatment approaches.

To Explore Nasal-Brain Lymphatic System for Brain-Targeted Drug Delivery and to Treat Neurodegenerative Diseases.

Brain-related Neurodegenerative Disorders (NDD) are the leading cause of low life expectancy globally. Brain-targeted drug delivery is required for treating most the NDD via bypassing the blood-brain barrier, and hepatic first-pass metabolism. The nasal-brain drug delivery route has the advantage of locally enhancing drug delivery to the brain, mainly through the olfactory route rather than systemic circulation. To overcome the limitations of nasal-brain drug delivery, a nanocarrier approach and mucoadhesive polymers are needed. Notwithstanding these constraints, various nanotechnology techniques have been created, including polymeric micelles, liposomes, polymeric nanoparticles, solid lipid nanoparticles, & nano-emulsions. This review aims to explore the intranasal pathway for drug delivery through the nasal-brain lymphatic systems, considering brain anatomy and physiology along with a drug formulation design approach.

Diagnosis, Management and Outcome of Truncus Arteriosus Communis Diagnosed during Fetal Life-Cohort Study and Systematic Literature Review.

Background/Objectives: Truncus arteriosus communis (TAC) is a rare congenital heart defect characterized by a single arterial trunk that supplies systemic, pulmonary, and coronary circulations. This defect, constituting approximately 1-4% of congenital heart diseases, poses significant challenges in prenatal diagnosis, management, and postnatal outcomes. Methods: A retrospective analysis was conducted at the local tertiary referral center on cases of TAC diagnosed prenatally between 2019 and 2024. Additionally, a systematic literature review was performed to evaluate the accuracy of prenatal diagnostics and the presence of associated anomalies in fetuses with TAC and compare already published data with the local results. The review included studies that especially described the use of fetal echocardiography, the course and outcome of affected pregnancies, and subsequent management strategies. Results: The analysis of local prenatal diagnoses revealed 14 cases. Of the 11 neonates who survived to birth, the TAC diagnosis was confirmed in 7 instances. With all seven neonates undergoing surgery, the intention-to-treat survival rate was 86%, and the overall survival rate was 55%. By reviewing published case series, a total of 823 TAC cases were included in the analysis, of which 576 were diagnosed prenatally and 247 postnatally. The presence of associated cardiac and extracardiac manifestations as well as genetic anomalies was common, with a 22q11 microdeletion identified in 27% of tested cases. Conclusions: Advances in prenatal imaging and early diagnosis have enhanced the management of TAC, allowing for the detailed planning of delivery and immediate postnatal care in specialized centers. The frequent association with genetic syndromes underscores the importance of genetic counseling in managing TAC. An early surgical intervention remains crucial for improving long-term outcomes, although the condition is still associated with significant risks. Long-term follow-up studies are essential to monitor potential complications and guide future management strategies. Overall, a coordinated multidisciplinary approach from prenatal diagnosis to postnatal care is essential for improving outcomes for individuals with TAC.

Animal life in the shallow subseafloor crust at deep-sea hydrothermal vents

It was once believed that only microbes and viruses inhabited the subseafloor crust beneath hydrothermal vents. Yet, on the seafloor, animals like the giant tubeworm Riftia pachyptila thrive. Their larvae are thought to disperse in the water column, despite never being observed there. We hypothesized that these larvae travel through the subseafloor via vent fluids. In our exploration, lifting lobate lava shelves revealed adult tubeworms and other vent animals in subseafloor cavities. The discovery of vent endemic animals below the visible seafloor shows that the seafloor and subseafloor faunal communities are connected. The presence of adult tubeworms suggests larval dispersal through the recharge zone of the hydrothermal circulation system. Given that many of these animals are host to dense bacterial communities that oxidize reduced chemicals and fix carbon, the extension of animal habitats into the subseafloor has implications for local and regional geochemical flux measurements. These findings underscore the need for protecting vents, as the extent of these habitats has yet to be fully ascertained.

Modern Aspects of Endovascular Thrombectomy of Acute Ischemic Stroke. Selection Criteria for Endovascular Thrombectomy. Prediction Of Treatment Outcomes

Endovascular thrombectomy (ET) effectively and safely recanalizes the occluded artery and restores the ischemic area in patients with acute ischemic stroke (IS), improving the clinical prognosis of stroke in the anterior and posterior circulation system, expanding the time therapeutic window from no more than 6 to 24 hours, greatly increasing the chances of functional independence and survival. However, some patients develop an unfavorable postoperative outcome, complications and “ineffectiveness” of revascularization. The thrombectomy result depends not only on the patient selection criteria, timing and success of the procedure, but on many other factors as well. Despite the advances in stroke treatment, the issues of neuroimaging and patient selection for ET remain relevant; the pathophysiological mechanisms of the influence of some factors on the effectiveness of the procedure are not completely clear; the causes of “uneffective” revascularization, unfavorable outcome and mortality after ET are unclear. An analysis of global experience in treating ischemic stroke with ET showed the heterogeneity of the patient selection criteria, clinical and neuroimaging variables, prognostic factors and treatment outcomes, which makes it difficult to draw a general conclusion and requires further targeted research. The article discusses the issues of patient selection, pathophysiological mechanisms of the influence of some risk factors on the outcome of ischemic stroke and the causes of unfavorable outcome and death after ET.

An In Vitro Platform for Pharmacokinetic Quantification and Optimization of Cerebrospinal Fluid Filtration and Drug Circulation

Abstract Background: Modification of cerebrospinal fluid (CSF) transport dynamics is an expanding method for treating central nervous system injury and diseases. One application of this route is to modify the distribution of solutes in the CSF, however few tools currently exist for this purpose. The present study describes the use of a subject-specific in-vitro CSF phantom to perform a parametric evaluation of the Neurapheresis? CSF Management System (NP) for both CSF filtration and intrathecal drug circulation. Methods: An in-vitro CSF phantom was constructed which included realistic anatomy for the complete subarachnoid space. This platform was configured to test multiple parametric modifications of a dual-lumen catheter and filtration system. Calibrated mapping of tracer distribution and area under the curve (AUC) measurements were used to compare filtration and intrathecal-circulation schemes using the NP device versus the clinical standards of care. Results: The NP device showed potential advantages over lumbar drain (LD) for clearance of simulated subarachnoid hemorrhage, especially in the spinal canal. Use of the NP device in combination with simulated intracerebroventricular drug infusion (ICV) resulted in an increased extent and uniformity of tracer spread compared to ICV alone. Conclusion: NP improved clearance of simulated subarachnoid hemorrhage compared to LD and increased uniformity of tracer concentration via simulated ICV, providing support for NP use in these scenarios. The in-vitro CSF phantom system presented here quantitatively described the effects of parametric boundary modification on solute distribution in the intrathecal space.

Assessment of a LPG hybrid solar dryer assisted with smart air circulation system for drying basil leaves

The fluctuation of solar radiation throughout the day presents a significant obstacle to the widespread adoption of solar dryers for the dehydration of agricultural products, particularly those that are sensitive to high temperatures, such as basil leaf drying during the winter season. Consequently, this recent study sought to address the limitations of solar-powered dryers by implementing a hybrid drying system that harnesses both solar energy and liquid petroleum gas (LPG). Furthermore, an innovative automatic electronic unit was integrated to facilitate the circulation of air between the drying chamber and the ambient environment. Considering the solar radiation status in Egypt, an LPG hybrid solar dryer has been developed to be suitable for both sunny and cloudy weather conditions. This hybrid solar dryer (HSD) uses indirect forced convection and a controlled auxiliary heating system (LPG) to regulate both temperature and relative humidity, resulting in increased drying rates, reduced energy consumption, and the production of high-quality dried products. The HSD was tested and evaluated for drying basil leaves at three different temperatures of50, 55, and 60 °C and three air changing rates of 70, 80, and 90%, during both summer and winter sessions. The obtained results showed that drying basil at a temperature of 60 °C and an air changing rate of 90% led to a decrease in the drying time by about 35.71% and 35.56% in summer and winter, respectively, where summer drying took 135–210 min and winter drying took 145–225 min to reach equilibrium moisture content (MC). Additionally, the effective moisture diffusivity ranged from 5.25 to 9.06 × 10− 9 m2/s, where higher values of effective moisture diffusivity (EMD) were increased with increasing both drying temperatures and air change rates. Furthermore, the activation energy decreased from 16.557 to 25.182 kJ/mol to 1.945–15.366 kJ/mol for the winter and summer sessions, respectively. On the other hand, the analysis of thin-layer kinetic showed that the Modified Midilli II model has a higher coefficient of determination R2, the lowest χ2, and the lowest root mean square error (RMSE) compared to the other models of both winter and summer sessions. Finally, the LPG hybrid solar dryer can be used for drying a wide range of agricultural products, and it is more efficient for drying medicinal plants. This innovative dryer utilizes a combination of LPG and solar energy, making it efficient and environmentally friendly.