Search Results (120)

Background/Objectives: Alzheimer’s disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed. Endothelin-1 (ET-1), a vasoconstrictive factor linked to cerebral vascular disease pathology and neuronal injury, could provide insights to better understand racial disparities in AD. As a potent vasoconstrictive peptide that regulates contractions in smooth muscle, endothelial cells, and pericytes, ET-1 may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, this may result in neuronal injury, contributing to the pathology of AD. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. In the United States (U.S.), ET-1 dysregulation in Hispanic/Latinx (H/L) ethnic populations has largely been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also require further investigation. In this study, we examined the role of the ET-1 protein in human plasma as a potential biomarker with predictive value for correlating with the development of AD by age, race, and sex. Methods: We examined ET-1 protein levels using quantitative mass spectrometry in AA and NHW patients with AD, along with controls. Results: A partial correlation between age at draw and ET-1, stratified by race and sex, while controlling for AD status, was significant for female AAs (r = 0.385, p = 0.016). When the data were not stratified but controlled for AD status, the partial correlation between age at draw and ET-1 was not significant (r = 0.108, p = 0.259). Conclusions: Based on the small number of plasma specimens and no plasma specimens from H/L individuals with AD, we conclude that ET-1 was clearly not a significant factor in predicting AD in this study and will require a larger scale study for validation. Full article

This review emphasises the importance of the cardiovascular response to facial cooling (FC) and breath holding in both sexes. The trigemino-cardiac reflex, triggered by FC, reduces heart rate (HR) and constricts blood vessels. When combined with breath holding, this effect intensifies, enhancing the cardiodepressive impact. The cardiovascular reaction to this combination, known as the cold-water face immersion or simulated diving test, varies among individuals and depends on their cardiovascular regulatory profiles, which differ between men and women. Despite extensive research on the cardiovascular response to FC and apnoea, most studies did not categorise participants by sex, leading to a limited understanding of how it influences trigeminal nerve stimulation (TGS) and breath-hold diving (BHD). Despite attempts to address this, the existing findings remain inconsistent due to intra- and inter-individual variability. Key factors influencing the diving response include the influence of the parasympathetic system on HR, vascular sympathetic activity affecting total peripheral resistance (TPR), sensitivity to CO₂, lung capacity, training, physical performance, duration of apnoea, and the stimulation of metaboreceptors in working muscles. These factors differ between men and women, potentially contributing to variations in the effectiveness of the response to the FC combined with breath holding. Full article

Background: Ankyloglossia is a congenital, abnormally short, thickened, or tight lingual frenulum that restricts tongue mobility, which may impair the development of the lower face morphology, namely the occlusion and skeleton. Objective: The aim of this study was to evaluate whether and how the lingual frenotomy benefits the occlusion and lower face skeleton development. Search methods and selection criteria: The authors, independently and in duplication, performed searches of PubMed, Cochrane Library, Medline, Web of Science, and Embase, introducing the following keywords: tongue tie, ankyloglossia, and short lingual frenum/frenulum, combined with malocclusion, lower face skeleton, and hyoid bone. Data collection and analysis: Relevant articles were assessed for quality according to the Cochrane guidelines and the data extracted for further analysis of the risk of bias and the evidence strength. Results: Seven articles including 1349 patients with ankyloglossia and 90 in the control group underwent the detailed analysis. The quality of the included studies was assessed as low. The strongest evidence of studies reporting the relationship of ankyloglossia with lower face abnormalities concerns the reduction in the intercanine and intermolar widths in either the maxilla or the mandible, as well as Class III occurrence. Limitations: The drawbacks of the analysed papers are mainly composition and number of participants. There is also a lack of good-quality prospective studies, particularly randomised clinical trials, in the literature. Conclusions: Although the lack of high-quality studies dictates that we must treat our results cautiously, the gathered evidence conditionally allow us to state the following: 1. ankyloglossia may be one of the factors contributing to maxillary constriction, Class III malocclusion, and mandibular incisor crowding; 2. the patient’s age is relevant when it comes to frenotomy timing. Possible indications for the procedure depend on the patient’s malocclusion. Full article

Background: Hydrogen sulfide (H₂S) is a gasotransmitter that modulates vascular tone, causing either vasodilation or vasoconstriction depending on the vascular bed, species, and experimental conditions. The cold-sensitive transient receptor potential ankyrin-1 (TRPA1) channel mediates H₂S-induced effects; however, its contribution to the vasomotor responses of different arteries at different temperatures has remained unclear. Here, we aimed to fill this gap by comparing the effects of sodium sulfide (Na₂S), which is a fast-releasing H₂S donor, on the isolated carotid and tail skin arteries of rats and mice at cold and normal body temperature with wire myography. Under the same circumstances, we also aimed to compare the effects of the canonical endothelium-dependent and -independent vasodilators, acetylcholine and sodium nitroprusside, respectively. Methods: We isolated the carotid and tail arteries from 32 adult Wistar rats and 64 TRPA1 knockout and wild-type mice, and then we studied their vasomotor responses to increasing doses (10⁻⁶–10⁻³ M) of Na₂S as well as to acetylcholine and sodium nitroprusside (10⁻⁵ M for both) at 37 °C and in cold (17 or 20 °C). Results: In rat vessels, Na₂S caused constriction of the carotids and relaxation of the tail arteries, which were not influenced by temperature. In mouse carotids, Na₂S caused vasorelaxation, which was more pronounced in the cold at a lower dose (10⁻⁴ M). At a higher dose (10⁻³ M), the dilation was markedly attenuated in the absence of the TRPA1 channel. In the mouse tail arteries, Na₂S caused vasorelaxation at 37 °C and vasocontraction in the cold. The genetic blockade of TRPA1 channels did not influence the vasomotor responses of the mouse tail arteries. Sodium nitroprusside-induced vasorelaxation was not influenced by any of the investigated factors, while acetylcholine-induced dilation decreased in the cold in all vessel types. Conclusions: Our results reveal the function of TRPA1 in the H₂S-induced dilation of carotid arteries in mice. We also highlight interspecies differences in the vasomotor responses between rats and mice, as well as the importance of the effect of temperature on vascular responses. The implementation of the identified variables in future research can advance our understanding of cardiovascular physiology, especially in conditions with hypothermia (either accidental or therapeutic). Full article

Multispectral transmission imaging has emerged as a promising technique for imaging breast tissue with high resolution. However, the method encounters challenges such as low grayscale, noisy transmission images with weak signals, primarily due to the strong absorption and scattering of light in breast tissue. A common approach to improve the signal-to-noise ratio (SNR) and overall image quality is frame accumulation. However, factors such as camera jitter and respiratory motion during image acquisition can cause frame misalignment, degrading the quality of the accumulated image. To address these issues, this study proposes a novel image registration method. A hybrid approach combining a genetic algorithm (GA) and a constriction factor-based particle swarm optimization (CPSO), referred to as GA-CPSO, is applied for image registration before frame accumulation. The efficiency of this hybrid method is enhanced by incorporating a squared constriction factor (SCF), which speeds up the registration process and improves convergence towards optimal solutions. The GA identifies potential solutions, which are then refined by CPSO to expedite convergence. This methodology was validated on the sequence of breast frames taken at 600 nm, 620 nm, 670 nm, and 760 nm wavelength of light and proved the enhancement of accuracy by various mathematical assessments. It demonstrated high accuracy (99.93%) and reduced registration time. As a result, the GA-CPSO approach significantly improves the effectiveness of frame accumulation and enhances overall image quality. This study explored the groundwork for precise multispectral transmission image segmentation and classification. Full article

This study proposes a positive pressure re-acceleration assisted seeding mechanism and analyzes the motion mechanism of corn seeds during the seeding process. By employing the CFD-EDEM gas-solid coupling simulation analysis method, the fluid characteristics, initial ejection velocity of seeds, seed dropping time difference, and sowing position difference in the seeding mechanism under different structural parameters of the air pressure valve body were investigated. The optimal structural parameters of the air pressure valve body were determined (nozzle gap c = 0.6 mm, throat constriction diameter d = 16 mm, and throat constriction length l = 44 mm). A multi-factor experimental method was used to explore the effects of airflow pressure, forward speed during sowing, and sowing distance on sowing performance, aiming to identify the optimal working parameters for the positive pressure re-acceleration seeding mechanism. High-speed camera technology was used to record and analyze the seed movement process. The results indicate that an increase in positive pressure within the seed guide tube shortens the sowing time of corn seeds, reduces the coefficient of variation of seed dropping time difference, and effectively improves the consistency of sowing distance. The optimal parameters are a forward speed of 8 km/h, sowing distance of 20 cm, airflow pressure of 10 kPa, with a sowing distance coefficient of variation of 7.56%, and a seed dropping time difference coefficient of variation of 5.35%. Full article

Oxidative stress emerges as a prominent factor in the onset and progression of intestinal inflammation, primarily due to its critical role in damaging cells and tissues. GABAergic signaling is important in the occurrence and development of various intestinal disorders, yet its effect on oxidative stress remains unclear. We attempted to assess whether GABAergic signaling participated in the regulation of oxidative stress during enteritis. The results showed that lipopolysaccharide (LPS) significantly decreased γ-aminobutyric acid (GABA) levels in the ileal tissues of mice. Interestingly, the application of GABA significantly repressed the shedding of intestinal mucosal epithelial cells and inflammatory cell infiltration, inhibited the expressions of proinflammatory factors, including granulocyte colony-stimulating factor and granulocyte-macrophage colony stimulating factor, and enhanced the levels of anti-inflammatory cytokines interleukin (IL)-4 and IL-10, indicating that GABA could alleviate enteritis in mice. This observation was further supported by transcriptome sequencing, revealing a total of 271 differentially expressed genes, which exhibited a marked enrichment of inflammatory and immune-related pathways, alongside a prominent enhancement of GABA B receptor (GABA_BR) signaling following GABA administration. Effectively, Baclofen pretreatment alleviated intestinal mucosal damage in LPS-induced mice, suppressed proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor alpha expressions, and boosted total antioxidant capacity, superoxide dismutase (SOD), and glutathione (GSH) levels. Moreover, Baclofen notably enhanced the viability of LPS-stimulated IPEC-J2 cells, contracted the proinflammatory secretion factors, and reinforced SOD, GSH, and catalase levels, emphasizing the anti-inflammatory and antioxidant effects associated with GABA_BR activation. Mechanistically, Baclofen restrained the mRNA and protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), and inducible nitric oxide synthase, while elevating nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 in both mice and IPEC-J2 cells, indicating that activating GABA_BR strengthened antioxidant abilities by interrupting the TLR4/MyD88/NLRP3 pathway. Furthermore, 16S rDNA analysis demonstrated that Baclofen increased the relative abundance of probiotic, particularly Lactobacillus, renowned for its antioxidant properties, while reducing the relative richness of harmful bacteria, predominantly Enterobacteriaceae, suggesting that GABA_BR signaling may have contributed to reversing intestinal flora imbalances to relieve oxidative stress in LPS-induced mice. Our study identified previously unappreciated roles for GABA_BR signaling in constricting oxidative stress to attenuate enteritis, thus offering novel insights for the treatment of intestinal inflammation. Full article

Conifer forests in Michoacán are facing climate change. Pinus devoniana Lindley, with natural distribution in the state, has shown certain adaptability, and knowing the influence of anatomy in the flow system is essential to delimit how it contributes to safety margins and water efficiency. For this, the pressure gradients in the cell lumens and their ramifications were analyzed by numerical simulations of flow throughout the real microstructure. Xylem were evaluated in radial, tangential and longitudinal directions. With the skeletonization of lumens and their constrictions, a branching system of interconnection between tracheids, ray cells, intercellular chambers, extensions, and blind pits were identified. In the simulation, the branched system bypasses the longitudinal fluid passage through the pores in membranes of pairs of pits to redirect it through the direct path branching, contributing to safety margins and water efficiency. Thus, resilience at low pressures because of the lower pressure drop in the extensions. The interface between the branching system and the cell lumens are sites of higher pressure gradient, more conducive to water-vapor formation or air leakage in the face of the lowest pressure system. The flow lines move along easy paths, regardless of the simulated flow direction. Deposits in the cell extensions were shown to be attached to the S3 layer of the cell wall, leaving the center of the duct free to flow. It is concluded that the spatial architecture of the xylem anatomy of Pinus dvoniana is a factor in the resilience at low pressures due to high water stress of the species. Full article

Background: Coronary microvascular dysfunction (CMD), characterised by a reduced coronary flow reserve (CFR) or an increased index of microcirculatory resistance (IMR), has received considerable attention as a cause of chest pain in recent years. However, the risks and causes of CMD remain unclear; therefore, effective treatment strategies have not yet been established. Heart failure or coronary artery disease (CAD) is a risk factor for CMD, with a higher prevalence among women. However, the other contributing factors remain unclear. In this study, we assessed the risk in patients with angina and non-obstructive coronary artery disease (ANOCA), excluding those with heart failure or organic stenosis of the coronary arteries. Furthermore, we analysed whether the risk of CMD differed according to component factors and sex. Methods: This study included 84 patients with ANOCA (36 men and 48 women; mean age, 63 years) who underwent coronary angiography and functional testing (CFT). The CFT included a spasm provocation test (SPT), followed by a coronary microvascular function test (CMVF). In the SPT, patients were mainly provoked by acetylcholine (ACh), and coronary spasm was defined as >90% transient coronary artery constriction on coronary angiography, accompanied by chest pain or ischaemic changes on electrocardiography. In 15 patients (18%) with negative ACh provocation, ergonovine maleate (EM) was administered as an additional provocative drug. In the CMVF, a pressure wire was inserted into the left anterior descending coronary artery using intravenous adenosine triphosphate, and the CFR and IMR were measured using previously described methods. A CFR < 2.0 or IMR ≥ 25 was indicative of CMD. The correlations between various laboratory indices and CMD and its components were investigated, and logistic regression analysis was performed, focusing on factors where p < 0.05. Results: Of the 84 patients, a CFR < 2.0 was found in 22 (26%) and an IMR ≥ 25 in 40 (48%) patients, with CMD identified in 46 (55%) patients. CMD was correlated with smoking (p = 0.020) and the use of EM (p = 0.020). The factors that correlated with a CFR < 2.0 included the echocardiograph index E/e′ (p = 0.013), which showed a weak but positive correlation with the CFR (r = 0.268, p = 0.013). Conversely, the factors correlated with an IMR ≥ 25 included RAS inhibitor usage (p = 0.018) and smoking (p = 0.042). Assessment of the risk of CMD according to sex revealed that smoking (p = 0.036) was the only factor associated with CMD in men, whereas the left ventricular mass index (p = 0.010) and low glycated haemoglobin levels (p = 0.012) were associated with CMD in women. Conclusions: Our results indicated that smoking status and EM use were associated with CMD. The risk of CMD differed between the two CMD components and sex. Although these factors should be considered when treating CMD, smoking cessation remains important. In addition, CMD assessment should be performed carefully when EM is used after ACh provocation. Further validation of our findings using prospective studies and large registries is warranted. Full article

The present study reports tongue configuration data recorded with ultrasound for two sets of consonant sequences uttered by five native Catalan speakers. Articulatory data for the onset cluster pairs [kl]-[ɣl] and [kɾ]-[ɣɾ], and also for [l#k]-[l#ɣ] and [r#k]-[r#ɣ], analyzed in the first part of the investigation revealed that, as a general rule, the (shorter) velar approximant is less constricted than the (longer) voiceless velar stop at the velar and palatal zones while exhibiting a more retracted tongue body at the pharynx. These manner of articulation-dependent differences may extend into the preceding liquid. Data for [k#l]-[kl] and [k#r]-[kɾ] dealt with in the second part of the study show that the velar is articulated with more tongue body retraction for [k#l] vs. [kl] and for [k#r] vs. [kɾ], and with a higher tongue dorsum for [k#l] vs. [kl] and the reverse for [k#r] vs. [kɾ]. Therefore, clusters are produced with a more extreme lingual configuration across a word boundary than in syllable-onset position, which at least in part may be predicted by segmental factors for the [k#r]-[kɾ] pair. These articulatory data are compared with duration data for all sequence pairs. Full article

Dashiling Gully, located in Miyun District, Beijing, exhibits a high susceptibility to debris flow due to its unique geological and topographical characteristics. The area is characterized by well-developed rock joints and fissures, intense weathering, a steep gradient, and a constricted gully morphology. These factors contribute to the accumulation of surface water and loose sediment, significantly increasing the risk of debris flow events. Following a comprehensive field geological investigation of Dashiling Gully, key parameters for simulation were obtained, including fluid weight, volume concentration, and rainfall. The formation and development conditions of potential mudslides were analyzed, and numerical simulations were conducted using FLO-2D software (version 2009) to assess scenarios with rainfall probabilities of 1 in 30, 50, and 100 years. The simulations accurately reconstructed the movement velocity, deposition depth, and other critical movement characteristics of mudslides under each rainfall scenario. Using ArcGIS, pre- and post-treatment hazard zoning maps were generated for Dashiling Gully. Furthermore, the efficacy of implementing a retaining wall as a mitigation measure was evaluated through additional numerical simulations. The results indicated that mudslide velocities ranged from 0 to 3 m/s, with deposition depths primarily between 0 and 3 m. The maximum recorded velocity reached 3.5 m/s, corresponding to a peak deposition depth of 4.31 m. Following the implementation of the retaining wall, the maximum deposition depth significantly decreased to 1.9 m, and high-risk zones were eliminated, demonstrating the intervention’s effectiveness. This study provides a rigorous evaluation of mudslide movement characteristics and the impact of mitigation measures within Dashiling Gully. The findings offer valuable insights and serve as a reference for forecasting and mitigating similar mudslide events triggered by heavy rainfall in gully mudslides. Full article

Collaborative multicenter research has significantly increased our understanding of fetal Ebstein anomaly, delineating risk factors for adverse outcomes as well as predictors of postnatal management. These data are incorporated into prenatal care and therapeutic strategies and inform family counseling and delivery planning to optimize care. This report details the translation of findings from multicenter studies into multidisciplinary prenatal care for a fetus with Ebstein anomaly, supraventricular tachycardia, and a circular shunt, including transplacental therapy to control arrhythmias and achieve ductal constriction, informed and coordinated delivery room management, and planned univentricular surgical palliation. Full article

People living with HIV (PLWH) face a growing burden of chronic diseases, owing to the combinations of aging, environmental triggers, lifestyle choices, and virus-induced chronic inflammation. The rising incidence of pulmonary vascular diseases represents a major concern for PLWH. The study of HIV-associated pulmonary vascular complications ideally requires a strong understanding of pulmonary vascular cell biology and HIV pathogenesis at the molecular level for effective applications in infectious diseases and vascular medicine. Active HIV infection and/or HIV proteins disturb the delicate balance between vascular tone and constriction, which is pivotal for maintaining pulmonary vascular health. One of the defining features of HIV is its high genetic diversity owing to several factors including its high mutation rate, recombination between viral strains, immune selective pressures, or even geographical factors. The intrinsic HIV genetic diversity has several important implications for pathogenic outcomes of infection and the overall battle to combat HIV. Challenges in the field present themselves from two sides of the same coin: those imposed by the virus itself and those stemming from the host. The field may be advanced by further developing in vivo and in vitro models that are well described for both pulmonary vascular diseases and HIV for mechanistic studies. In essence, the study of HIV-associated pulmonary vascular complications requires a multidisciplinary approach, drawing upon insights from both infectious diseases and vascular medicine. In this review article, we discuss the fundamentals of HIV virology and their impact on pulmonary disease, aiming to enhance the understanding of either area or both simultaneously. Bridging the gap between preclinical research findings and clinical practice is essential for improving patient care. Addressing these knowledge gaps requires interdisciplinary collaborations, innovative research approaches, and dedicated efforts to prioritize HIV-related pulmonary complications on the global research agenda. Full article

Coatomer Protein Complex-II (COPII) mediates anterograde vesicle transport from the endoplasmic reticulum (ER) to the Golgi apparatus. Here, we report that the COPII coatomer complex is constructed dependent on a small GTPase, Sar1, in spermatocytes before and during Drosophila male meiosis. COPII-containing foci co-localized with transitional endoplasmic reticulum (tER)-Golgi units. They showed dynamic distribution along astral microtubules and accumulated around the spindle pole, but they were not localized on the cleavage furrow (CF) sites. The depletion of the four COPII coatomer subunits, Sec16, or Sar1 that regulate COPII assembly resulted in multinucleated cell production after meiosis, suggesting that cytokinesis failed in both or either of the meiotic divisions. Although contractile actomyosin and anilloseptin rings were formed once plasma membrane ingression was initiated, they were frequently removed from the plasma membrane during furrowing. We explored the factors conveyed toward the CF sites in the membrane via COPII-mediated vesicles. DE-cadherin-containing vesicles were formed depending on Sar1 and were accumulated in the cleavage sites. Furthermore, COPII depletion inhibited de novo plasma membrane insertion. These findings suggest that COPII vesicles supply the factors essential for the anchoring and/or constriction of the contractile rings at cleavage sites during male meiosis in Drosophila. Full article

Heart failure and cancer are currently the deadliest diseases in the Western world, posing the most pressing clinical challenges that remain unmet today. Both conditions share similar risk factors, including age, genetics, lifestyle, chronic inflammation, stress, and more. Furthermore, medications that are being used to counteract cancer frequently result in cardiotoxicity and the spontaneous emergence of heart failure. Thus, heart failure and cancer display an intimate connection and share similarities. Recent studies show that cardiac remodeling and heart failure promote cancer progression and metastasis. Using three different mouse models for heart failure revealed that the communication between the remodeled heart and the tumor is facilitated through multiple secreted factors. Among these factors, Periostin was consistently found to be elevated in all models and was shown to be required in vitro. Yet, whether Periostin is necessary for tumor promotion in vivo is unknown. Towards this end, we examined tumor promotion in mice lacking Periostin following transverse aortic constriction (TAC). Despite the loss of Periostin, tumor growth was promoted in the TAC-operated mice. This likely occurred due to increased levels of various cytokines and growth factors in Periostin KO mice. Many of these factors are potential ligands of Integrin receptors. Therefore, we next studied the role of Integrin receptors in the tumor-promotion phenotype following heart failure. We generated cancer cells with an Integrin β1 loss of function mutation and examined tumor growth in the presence and absence of heart failure. Integrin β1 KO cancer cells fail to display cardiac-remodeling-dependent tumor-promotion. Interestingly, a previous study showed that renal cell carcinoma cells (Renca) fail to be promoted following a myocardial infarction. Consistently, we show that Renca cells do not respond to secreted factors derived from the failing heart both in vitro and in vivo. Interestingly, Renca cells display low basal mRNA levels of Integrin β1 which may explain the inability of heart failure to promote their growth. The findings may have significant clinical relevance to cardio–oncology patients who suffer from cancers with high levels of Integrin β1. Chemotherapy leading to cardiotoxicity in these patients may generate a vicious cycle with poor prognosis. Full article