Search Results (231)

This study investigates the influence of weaving process parameters on the structural homogeneity of woven fabrics, with a focus on the structural autoregulation phenomenon. Two experimental fabric groups of 30 each, plain and twill weaves, were produced using varied loom settings: shed closure timing, lease rod position, backrest roller position, warp pre-tension, and yarn twist direction. Structural uniformity was assessed using a proprietary method and the MagFABRIC 2.1. image analysis system, which quantify intra-repeat, inter-repeat, and global inhomogeneity. This method uses the size, shape, and location of inter-thread pores as well as warp and weft pitches. The results indicate that autoregulation can reduce local structural disturbances, including warp yarn grouping. In plain weaves, loom parameters and humidity significantly contributed to structural autoregulation. In contrast, twill weaves demonstrated dominant internal feedback mechanisms, significantly influenced by yarn twist direction. Regression models at F = 10 revealed nonlinear interactions, confirming autoregulation and experimentally supporting Nosek’s quasi-dynamic theory for these types of fabrics. The results of these studies have practical relevance in high-performance textiles such as filtration, barrier fabrics, and composite reinforcements, where local structural deviations critically affect the functional properties of fabrics. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Backgrounds/Objective: The impact of metabolic disturbances induced by an unbalanced diet on cognitive decline in mid-life is now widely observed, although the mechanisms are not well identified. Here we report that glutamatergic vasoactive pathways are a key feature of high-fat-diet (HFD)-induced neurogliovascular uncoupling in mice. Methods: C57Bl6/J mice are fed either with normal diet (ND) or high-fat diet (HFD) during 6 or 12 months and characterized for metabolic status. Cerebral vascular tree from pial to intraparenchymal arteries, is investigated with Halpern’s arteriography and with differential interference contrast infrared imaging of brain slices. Results: A 70% alteration in the myogenic tone of the basilar artery is observed as early as 6 months (M6) after the HFD. Infrared imaging revealed a 77% reduction in the glutamate-induced vasodilation of intraparenchymal arterioles appearing after 12 months (M12) of the HFD. The respective contributions of enzymes involved in glutamatergic pathways were altered as a function of HFD and time. The decrease in astrocytic COX I observed at M6 was followed by a loss of neuronal COX II and a compensatory action of NOS at M12. Conclusions: This HFD-induced neurogliovascular uncoupling pathway offers therapeutic targets to consider for improving cerebral vasoactive functions while preventing peripheral metabolic disturbances. Full article

Cardiovascular diseases (CVDs) are the leading causes of death worldwide, and most of them are connected with atherosclerosis (AS). Hypertension (HT), hyperlipidemia (HPL), and hyperglycaemia (HG) are the main risk factors responsible for CVD and have become a significant public health issue. AS might be a prime causative factor in CVD, and it originates from endothelial cell dysfunction. On the other hand, the factors mentioned above might cause endothelial cell damage as a consequence of endothelial dysfunction (ED) or might be regarded as a consequence of ED. Thus, endothelial cells are critical for maintaining vascular health and homeostasis, and their function is a key contributor to the initiation and progression of AS. The autoregulation of microcirculation, which is functionally present in the brain and kidneys, and from the physiological and pathophysiological point of view, is of high importance to preserve the proper function of the endothelium of blood vessels. The key factor responsible for cardiovascular system regulation and proper action is nitric oxide (NO). Disturbances in NO synthesis and/or bioavailability, caused by oxidative stress and/or inflammation, accompany or even precede diseases such as HT, angiogenesis-associated disorders, HPL, and HG, which are on the pathway of AS development. In the present review, we attempted to synthesize recent advances in understanding the pathophysiology of multifactorial-related AS. Full article

Intracranial pressure (ICP) pulse wave morphology, including the ratios of the three characteristic peaks (P1, P2, and P3), offers valuable insights into intracranial dynamics and brain compliance. Traditional invasive methods for ICP pulse wave monitoring pose significant risks, highlighting the need for non-invasive alternatives. This pilot study investigates a novel non-invasive method for monitoring ICP pulse waves through closed eyelids, using a specially designed, liquid-filled, fully passive sensor system named ‘Archimedes 02’. To our knowledge, this is the first technological approach that enables the non-invasive monitoring of ICP pulse waveforms via closed eyelids. This study involved 10 healthy volunteers, aged 26–39 years, who underwent resting-state non-invasive ICP pulse wave monitoring sessions using the ‘Archimedes 02’ device while in the supine position. The recorded signals were processed to extract pulse waves and evaluate their morphological characteristics. The results indicated successful detection of pressure pulse waves, showing the expected three peaks (P1, P2, and P3) in all subjects. The calculated P2/P1 ratios were 0.762 (SD = ±0.229) for the left eye and 0.808 (SD = ±0.310) for the right eye, suggesting normal intracranial compliance across the cohort, despite variations observed in some individuals. Physiological tests—the Valsalva maneuver and the Queckenstedt test, both performed in the supine position—induced statistically significant increases in the P2/P1 and P3/P1 ratios, supporting the notion that non-invasively recorded pressure pulse waves, measured through closed eyelids, reflect intracranial volume and pressure dynamics. Additionally, a transient hypoemic/hyperemic response test performed in the upright position induced signal changes in pressure recordings from the ‘Archimedes 02’ sensor that were consistent with intact cerebral blood flow autoregulation, aligning with established physiological principles. These findings indicate that ICP pulse waves and their dynamic changes can be monitored non-invasively through closed eyelids, offering a potential method for brain monitoring in patients for whom invasive procedures are not feasible. Full article

ECF σ factors, which constitute the most abundant and diverse group of the σ⁷⁰-family, are important signal response regulatory proteins in bacterial adaptative responses to harsh environmental changes and for bacterial survival. Their activity is commonly controlled by specific and reversible interactions with their cognate anti-σ factors (soluble or transmembrane proteins), which directly or indirectly sense the environmental signals and transmit them to their partner σ factor. The genome of pathogenic L. interrogans is predicted to encode 11 ECF σ^E-type factors and more than 30 regulators predicted as anti-σ factors, anti-anti-σ factors, and regulators of anti-anti-σ factors. We have recently demonstrated that one of the L. interrogans ECF σ factors, i.e., LIC_12757, indeed functions as a transcriptional factor and is autoregulated at the transcriptional level. This study is a next step towards determining key aspects of LIC_12757 functioning in Leptospira. By using genetic and proteomic approaches, we provide strong evidence that the LIC_12757 activity is controlled via interactions with its putative FecR-like regulator, LIC_12756. We also demonstrate that LIC_12756 exhibits not only an anti-σ activity but also acts as a positive regulator of LIC_12757 in the presence of specific environmental cues. Interestingly, we found that the nutrient-limiting conditions, including iron deficiency, may act as specific signals for the LIC_12757 activation. In conclusion, we identified the L. interrogans regulatory system consisting of an ECF σ factor, LIC_12757, and a FecR-like regulator, LIC_12756, which is most likely involved in the response of pathogenic Leptospira to iron and nutrient limitation, and thus also likely involved in their response to host-induced stress. Full article

Ketone bodies (KBs) serve as an alternative energy source for healthy and failing hearts and have important effects on myocardial blood perfusion in both physiological and pathological states. Early animal studies suggest that KBs may provide protective benefits in ischemic heart disease and heart failure. Under normal circumstances, coronary blood flow regulation is an intricate system with contributions from metabolic, autonomic, compressive, and endothelial factors, with the metabolic regulatory pathway being the most significant contributor. We conducted a non-systematic review of studies published between 1987 and 2024. In this review, we explored the physiological autoregulation of normal coronary blood flow, the role of ketone bodies in myocardial perfusion in health and disease, and the potential role of exogenous ketone body supplementation in producing salutary effects on myocardial blood flow (MBF) and metabolism in exercise and cardiac disease states including ischemia, heart failure, and the aging heart. Overall, our findings demonstrated that KBs improve MBF and ejection fraction in healthy human subjects and have beneficial effects on cardiac output and left heart filling pressures in patients with decompensated heart failure. Although resting myocardial blood flow decreases with age, further studies are required to assess the impact of KBs on MBF in aging populations. Additionally, more research is needed to investigate the effects of KBs during exercise and in instances of myocardial ischemia. Full article

Continuous metrics of cerebral autoregulation (CA) assessment have been developed using various multimodal cerebral physiological monitoring devices. However, CA regional disparity remains unclear in states of health and disease. Leveraging existing archived data sources, we preliminarily evaluated regional hemispheric disparity in CA using the near infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx/COx-a). Along with bilateral NIRS, regional cerebral oxygen saturation, arterial blood pressure, cerebral perfusion pressure, and bilateral COx/COx-a were derived using three different temporal resolutions—10 s, 1 min, and 5 min—based on non-overlapping mean values. The regional disparity between hemispheres was evaluated based on median and median absolute deviation. Further, patient-level autoregressive integrative moving average models were calculated for each signal stream and used to generate personalized vector autoregressive models. Multi-variate cerebral physiologic relationships between hemispheres were assessed via impulse response functions and Granger causality analyses. Data from 102 healthy control volunteers, 27 spinal surgery patients, and 95 TBI patients (varying in frontal lobe pathology impacting the optode path; 64 without bifrontal lobe pathology, 15 without left frontal lobe pathology, 11 without right frontal lobe pathology, and 5 with bifrontal lobe pathology) were retrospectively analyzed. For subjects with or without cranial pathology, no difference in COx/COx-a was found between hemispheres regardless of the analytic method. In TBI patients without pathology underneath the NIRS sensor, distant parenchymal injury does not seem to have an effect on the CA of uninjured frontal lobes. Further work is required to characterize regional disparities with multi-channel CA measurements in healthy and disease states. Full article

Background: Preeclampsia (PE) and eclampsia are characterized by changes in cerebral hemodynamics, which may result in serious and even life-threatening neurological complications. The aim of the present work was to compare cerebral hemodynamic changes during the roll-over test in women with mild and severe PE. Patients and methods: Healthy pregnant and PE women in their third trimester were studied. Transcranial Doppler (TCD) measurements of the right middle cerebral artery (MCA) were performed in the left lateral position and 5 min after turning to the supine position (roll-over test = ROT). Besides cerebral blood flow measurements, the blood pressure was measured in the right arm using a standard mercury sphygmomanometer. An independent gynecologist categorized the preeclamptic patients into mild and severe groups based on the clinical and laboratory results. The TCD assessors were unaware of the patient grouping while performing the TCD and blood pressure measurements. Results: A total of 21 healthy pregnant females (mean age: 26.1 ± 5.1 yrs), 11 females with mild PE (28.2 ± 6.8 yrs), and 18 females with severe PE (29 ± 7.4 yrs) were studied. A significant increase in the mean arterial pressure was observed in all of the groups during the roll-over test: healthy pregnant patients: from 106.3 ± 16.3 to 113.8 ± 15.9 mmHg; patients with mild PE: from 100 ± 11.2 to 110 ± 8.7 mmHg; and patients with severe PE: from 106.3 ± 16.3 to 113.8 ± 15.8 mmHg. The MCA mean blood flow velocities in the left lateral position were significantly lower in the control patients than in those with PE: MCAV control: 71.2 ± 12.7 cm/s; mild PE: 78.2 ± 19.4 cm/s; and severe PE: 96 ± 15.6 cm/s, p < 0.001. Turning to the supine position resulted in a decrease in the MCAV in all of the groups, but the differences between the groups remained unchanged: controls: 69.5 ± 9.1 cm/s; mild PE: 75.7 ± 17.5 cm/s; and severe PE: 85.7 ± 18.4 cm/s, respectively, p = 0.014. A slight but statistically insignificant increase in the pulsatility index was observed in all of the groups. Conclusions: This is the first study comparing cerebral hemodynamic changes in healthy pregnant females and in those with mild and severe PE during a roll-over test. Changing the posture did not result in changes in the cerebral blood flow velocities in the healthy and preeclamptic pregnant patients. Our results indicate that static cerebral autoregulation is preserved both in the mild and severe preeclamptic patients. Full article

Alternative splicing is essential for the generation of various protein isoforms that are involved in cell differentiation and tissue development. In addition to internal coding exons, alternative splicing affects the exons with translation initiation codons; however, little is known about these exons. Here, we performed a systematic classification of human alternative exons using coding information. The analysis showed that more than 5% of cassette exons contain translation initiation codons (alternatively skipped exons harboring a 5′ untranslated region and coding region, 5UC-ASEs) although their skipping causes the deletion of translation initiation sites essential for protein synthesis. The splicing of 5UC-ASEs is under the repressive control of MATR3, a DNA/RNA-binding protein associated with neurodegeneration, and is distinctly regulated particularly in the human brain, muscle, and testis. Interestingly, MATR3 represses its own translation by skipping a 5UC-ASE in MATR3 to autoregulate its expression level. 5UC-ASEs are larger than other types of alternative exons. Furthermore, evolutionary analysis revealed that 5UC-ASEs have already appeared in cartilaginous fishes, have increased in amphibians, and are concentrated in the genes involved in transcription in mammals. Taken together, our analysis identified a unique set of alternative exons, 5UC-ASEs, that have evolutionarily acquired a repression mechanism for gene expression through association with MATR3. Full article

Traumatic brain injury (TBI) causes multiple cerebrovascular disruptions and oxidative stress. These pathological mechanisms are often accompanied by serious impairment of cerebral blood flow autoregulation and neuronal and glial degeneration. Background/Objectives: Multiple biochemical cascades are triggered by brain damage, resulting in reactive oxygen species production alongside blood loss and hypoxia. However, most currently available early antioxidant therapies lack capacity and hence sufficient efficacy against TBI. The aim of this study was to test a novel catalytic antioxidant nanoparticle to alleviate the damage occurring in blast TBI. Methods: TBI was elicited in an open blast rat model, in which the rats were exposed to the effects of an explosive blast. Key events of the post-traumatic chain in the brain parenchyma were studied using immunohistochemistry. The application of a newly developed biologically compatible catalytic superoxide dismutase mimetic carbon-based nanocluster, a poly-ethylene-glycol-functionalized hydrophilic carbon cluster (PEG-HCC), was tested post-blast to modulate the components of the TBI process. Results: The PEG-HCC was shown to significantly ameliorate neuronal loss in the brain cortex, the dentate gyrus, and hippocampus when administered shortly after the blast. There was also a significant increase in endothelial activity to repair blood–brain barrier damage as well as the modulation of microglial and astrocyte activity and an increase in inducible NO synthase in the cortex. Conclusions: We have demonstrated qualitatively and quantitatively that the previously demonstrated antioxidant properties of PEG-HCCs have a neuroprotective effect after traumatic brain injury following an explosive blast, acting at multiple levels of the pathological chain of events elicited by TBI. Full article

The head-up tilt (HUT) test assesses both cardiovascular autonomic regulation and cerebral autoregulation. This exploratory study examined age-related changes in cardiovascular and cerebrovascular responses during the HUT test in three healthy cohorts (young, middle-aged, and elderly). We recruited 2342 neurologist-diagnosed ‘normal’ individuals from 18 June 2014 to 25 February 2022. Cerebrovascular and cardiovascular responses were assessed during the HUT test, including cerebral blood flow velocity (CBFv) of the middle cerebral artery, systolic arterial pressure (SYS), diastolic arterial pressure (DIA), mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), stroke volume (SV), cardiac output (CO), and cerebrovascular conductance (CVCi). These variables were analyzed across three groups (young, middle-aged, and elderly) and three periods (resting, post-HUT, and recovery). Participants were stratified into three age groups: young (18–45 years; n = 384), middle-aged (46–59 years; n = 434), and elderly (≥60 years; n = 590). PP increased significantly with age, while CBFv and CVCi decreased significantly across the three periods. As measurements progressed, DIA and HR increased, and SV, CBFv, and CVCi decreased. This study enhances our understanding of age-related differences in cardiovascular and cerebrovascular responses to the HUT test. These insights may improve the clinical utility of the HUT test and guide outcome analysis across age groups. Full article

Objectives: Blood pressure (BP) management is challenging in patients with acute ischemic supratentorial stroke undergoing recanalization therapy due to the lack of established guidelines. Assessing dynamic cerebral autoregulation (dCA) may address this need, as it is a bedside technique that evaluates the transfer function phase in the very low-frequency (VLF) range (0.02–0.07 Hz) between BP and cerebral blood flow velocity (CBFV) in the middle cerebral artery. This phase is a prognostically relevant parameter, with lower values associated with poorer outcomes. This study aimed to evaluate whether early cranial computed tomography perfusion (CTP) can predict this parameter. Methods: In this retrospective study, 165 consecutive patients with hemispheric strokes who underwent recanalizing therapy were included (median age: 73 years; interquartile range (IQR) 60–80; women: 43 (26%)). The cohort comprised 91 patients treated with intravenous thrombolysis (IV-lysis) alone (median National Institute of Health Stroke Scale (NIHSS) score: 5; IQR 3–7) and 74 patients treated with mechanical thrombectomy (median NIHSS: 15; IQR 9–18). Regression analysis was performed to assess the relationship between pretreatment CTP-derived ischemic penumbra and core stroke volumes and the dCA VLF phase, as well as CBFV assessed within the first 72 h post-stroke event. Results: Pretreatment penumbra volume was a significant predictor of the VLF phase (adjusted r² = 0.040; β = −0.001, 95% confidence interval (CI): −0.0018 to −0.0002, p = 0.02). Core infarct volume was a stronger predictor of CBFV (adjusted r² = 0.082; β = 0.205, 95% CI: 0.0968–0.3198; p = 0.0003) compared to penumbra volume (p = 0.01). Additionally, in the low-frequency range (0.07–0.20 Hz), CBFV and BP were inversely related to the gain, an index of vascular tone. Conclusion: CTP metrics appear to correlate with the outcome-relevant VLF phase and reactive hyperemic CBFV, which interact with BP to influence vascular tone and gain. These aspects of dCA could potentially guide BP management in patients with acute stroke undergoing recanalization therapy. However, further validation is required. Full article

Sepsis-associated encephalopathy (SAE) is linked to high mortality and impaired neurologic outcome. Brain ultrasonography (US) is a non-invasive tool for cerebral monitoring. A scoping review of the literature in three databases was performed to answer if brain perfusion is altered in sepsis, to determine the role of brain US in guiding resuscitation and its ability to predict the outcome. Randomized controlled trials, clinical trials, observational studies, and systematic reviews on adults with sepsis or septic shock in the ICU were included. A total of 625 articles were screened, and 34 included. There were 85% observational studies and 15% systematic reviews with or without meta-analysis. The majority of studies had a small sample size and used different metrics. The studies focused on cerebral blood flow (CBF) alterations reporting variable results (CBF increased, normal, or decreased). The findings showed a variable rate of cerebral autoregulation (CAR) impairment, with higher incidence in the early stages of sepsis and associations with poor neurological outcomes. However, the impact of CAR and CBF alterations on neurological outcomes and mortality was not clear. Very few studies were found on resuscitation. In conclusion, brain US can identify cerebral perfusions alterations and its usage in sepsis is promising. However, the current body of evidence for its usage is poor and lacks standardization. Full article

Cerebral hyperperfusion syndrome (CHS) is a serious post-procedural complication of carotid artery stenting (CAS). The pathophysiological mechanisms of CHS in the absence of arterial hypertension (AH) remain only partially understood. We performed a systematic literature search of the PubMed database using the terms »cerebral hyperperfusion syndrome«, »hypotension«, »hyperperfusion«, »stroke«, »intracranial hemorrhages«, »risk factors«, »carotid revascularization«, »carotid stenting«, »carotid endarterectomy«, »blood-brain barrier«, »endothelium«, »contrast encephalopathy«, and combinations. We present a case of a normotensive female patient who developed CHS post-CAS for symptomatic carotid stenosis while being hypotensive with complete recovery. We identified 393 papers, among which 65 were deemed relevant to the topic. The weighted average prevalence of CHS after CAS is 1.2% [0.0–37.7%] with that of intracranial hemorrhage (ICH) being 0.51% [0–9.3%]. Recently symptomatic carotid stenosis or contralateral carotid revascularization, urgent intervention, acute carotid occlusion, contralateral ≥70% stenosis, and the presence of leptomeningeal collaterals were associated with CHS. A prolonged hemodynamic instability after CAS conveys a higher risk for CHS. However, none of the articles mentioned isolated hypotension as a risk factor for CHS. Whereas mortality after ICH post-CAS ranges from 40 to 75%, in the absence of ICH, CHS generally carries a good prognosis. AH is not obligatory in CHS development. Even though impaired cerebral autoregulation and post-revascularization changes in cerebral hemodynamics seem to play a pivotal role in CHS pathophysiology, our case highlights the complexity of CHS, involving factors like endothelial dysfunction and sudden reperfusion. Further research is needed to refine diagnostic and management approaches for this condition. Full article